cancer-brain-metastasis

がん脳転移 MOC

全がん種における脳転移・軟膜転移の機序、治療、biomarker を統合する。BBB 動態、neural niche、CNS-active 薬剤、放射線療法との併用戦略を含む。

ドメイン定義

含む: 脳実質転移・軟膜転移の biology (BBB / BTB の構造変化、CTC による関門突破、neural niche、astrocyte / 骨髄系-tumor crosstalk、脈絡叢 pre-metastatic niche、脳特異的代謝適応 (acetate-ACSS2-ferroptosis 耐性・酸化的リン酸化 (oxidative phosphorylation; OXPHOS) シフト))、脳転移発症の分子機序、神経-免疫軸、CNS-active (中枢神経系 central nervous system 移行性) TKI (tyrosine kinase inhibitor; osimertinib, alectinib, lorlatinib 等)、放射線 (定位放射線手術 stereotactic radiosurgery; SRS, 全脳照射 whole-brain radiotherapy; WBRT) との併用、脳転移特異的 biomarker、肺がん以外の脳転移 (乳がん、メラノーマ等) も含む。

含まない: 脳原発腫瘍 (glioma, meningioma 等) の単独病態、軟膜炎症性疾患 (多発性硬化症等)、脳転移の治療効果単独の臨床試験 (→ lung-cancer-treatment の subgroup として)。

現状の合意 (State of the Field)

BBB / BTB の再編と CTC による関門突破: 脳転移は肺がん (特に EGFR/ALK driver 陽性の非小細胞肺がん non-small cell lung cancer; NSCLC、小細胞肺がん small cell lung cancer; SCLC)、乳がん (HER2 陽性、三重陰性乳がん triple-negative breast cancer; TNBC)、メラノーマで高頻度に発生し、NSCLC では診断時に約 15%、経過中に最大 40% が脳転移を発症する主要な予後規定因子である (Mavrikios et al. AnnOncol 2026)。基盤となる血液脳関門 (BBB) はタイトジャンクション・周皮細胞・アストロサイト終足からなる neurovascular unit として機能するが、転移進展に伴い構造的・機能的に再編され「血液腫瘍関門 (BTB)」へ変化する (Boire et al. NatRevCancer 2020 / Achrol et al. NatRevDisPrimers 2019)。循環腫瘍細胞 (CTC) の血管外漏出には CD44 高発現幹細胞由来の GPR124 高発現周皮細胞様細胞による trans-endothelial migration が関与し (Huang et al. CancerCell 2023)、近年は CTC 分泌 GPNMB が内皮 EGFR を CBL 依存性に分解し、FTO 抑制を介した YTHDF2/TJP1 の m6A 修飾亢進でタイトジャンクションを解体する分子連鎖が同定された (Liu et al. CancerDiscov 2026)。EV 由来の TGFβ1-lnc-MMP2-2 軸も BBB 透過性を高めて脳転移を促す (Wu et al. CellDeathDis 2021)。BTB は “leaky but not open” の不均一な透過性を示し、薬剤到達の不均一性が耐性クローン選択を促進する (詳細は BBB-disruption-in-brain-metastasis / 既存 Output brain-metastasis-srs-io-sequencing)。

脳転移 niche を駆動する細胞 — astrocyte / 骨髄系 / 神経軸: 反応性 astrocyte は STAT3 をノードに PD-L1・TIMP1・TRAIL・TGFβ・IL-10 等を誘導し、T 細胞と骨髄系の双方を抑制する免疫抑制的境界を形成し、その STAT3 を標的とする silibinin は臨床試験 (NCT05689619) で脳転移増殖の制御と CD8 T 細胞応答の増強を示して astrocyte-免疫軸の治療標的化に臨床的端緒を与えた (Faust et al. NatImmunol 2026)。未治療 NSCLC 脳転移の単一核・空間ゲノム解析では、染色体不安定性 (CIN) が原発巣より顕著に高く、神経様メタプログラム (MP7/8) と EMT を共発現する希少な脱分化集団「cluster 21」(全悪性細胞の 1.81%) が脳転移特異的に濃縮し、CD8 T 細胞減少・CD163 高発現 M2 マクロファージ・好中球を伴う免疫抑制微小環境が形成される (Tagore et al. NatMed 2025)。好中球は脳腫瘍微小環境で局所的に活性化し (Maas et al. Cell 2023)、脳転移は neural circuit へ与える影響でサブタイプ分類が可能である (Sanchez-Aguilera et al. CancerCell 2023)。さらに肺腺がんが Npy2r+/Trpv1+ 迷走神経感覚ニューロンを乗っ取り脳幹 RVLM 経由で交感神経 β2 アドレナリンシグナルを駆動し、肺胞マクロファージの ARG1 化を介して全身性に抗腫瘍免疫を抑制する双方向の腫瘍-脳神経回路が示され、β遮断薬・神経標的の re-purposing に理論的根拠を与えた (Wei et al. Nature 2026)。GPNMB は脳転移特異的な内皮-免疫 interactome を再編し、CXCL12-CXCR4 軸を介した未成熟リンパ系凝集と時間依存的 T 細胞疲弊を促す (Liu et al. CancerDiscov 2026)。

Tumor-derived EV による pre-metastatic niche conditioning と liquid biopsy: 腫瘍由来細胞外小胞 (EV) は遠隔関門を事前 conditioning する central mediator であり、Hoshino らの integrin paradigm のように CEMIP 等の EV 表面分子が脳転移 organotropism を規定する (Rodrigues et al. NatCellBiol 2019)。軟膜転移では癌細胞由来 EV がセロトニン代謝産物 5-HIAA を脈絡叢血管内皮へ選択的に送達し、AHR 経路活性化を介して Cav1 上昇・VE-cadherin/ZO-1 低下による血管透過性亢進を起こし、癌細胞が脈絡叢へ到達する前から関門を permissive 化することが示された — 脳脊髄液 (cerebrospinal fluid; CSF) 中 5-HIAA は軟膜転移 (leptomeningeal metastasis; LM) 患者で有意に上昇し診断バイオマーカー候補となる (Huang et al. NatCancer 2026)。Liquid biopsy 軸では CSF ctDNA / EV-based assay が plasma ctDNA 陰性となる CNS-only progression を補完する役割が成熟しつつある (詳細は Liquid-biopsy-paradigm / 既存 Output ev-liquid-biopsy-clinical-implementation)。

脳転移特異的な免疫回避と ICI / SRS+IO sequencing: NSCLC 脳転移は HLA class-I 抗原提示機構 (APM; β2M / PSMB9 / PSMB10 / TAP1/2 / Tapasin) が原発巣より広範に低下し、しかも pSTAT1/IRF1 が保持された IFNγ 非依存的な機序で生じることが多コホート TMA と H2030-BrM3 体外モデルで実証され、PD-L1 単独評価では頭蓋内免疫回避を捉えきれないことが明らかになった (Vilarino et al. MolCancer 2026)。一方で「脳は一様に immune cold」という旧来観は覆されつつあり、乳がん脳転移では CD8+ 組織常在記憶 (TRM) 様細胞高浸潤と三次リンパ構造 (TLS) という相互にほぼ重複しない 2 つの予後良好免疫ニッチが同定され (それぞれ独立予後因子、ハザード比 hazard ratio; HR 約 0.5)、PD-1/TIGIT 二重遮断が自家オルガノイドで腫瘍殺傷を増強した (Jassowicz et al. CancerCell 2026 / Yuan et al. CancerCell 2026)。組織学的浸潤様式 (高浸潤 HI vs 低浸潤 MI) でも免疫景観が二分し、反応性アストロサイト由来 CHI3L1 が高浸潤型の免疫冷環境と抗 PD-1 抵抗性を駆動する ICI (免疫チェックポイント阻害薬 immune checkpoint inhibitor) 反応性バイオマーカー候補として浮上した (Maritan et al. JCIInsight 2026)。臨床的には非 oncogene-addicted NSCLC で ICB (免疫チェックポイント遮断 immune checkpoint blockade) 単剤の頭蓋内奏効率 (objective response rate; ORR) は限定的 (PD-L1≥1% で約 30%) だが化学免疫療法で IC-ORR 40-78% へ向上し、SRS+ICI sequencing は放射線壊死 (radiation necrosis; RN) リスクと synergy のトレードオフが central debate である (Mavrikios et al. AnnOncol 2026、本 MOC 由来 brain-metastasis-srs-io-sequencing / SRS-ICI-radiation-necrosis で詳述)。

脳特異的代謝環境への適応 — acetate / OXPHOS / ferroptosis 耐性: 脳実質は acetate が豊富で脂質制限的という特異な代謝環境をもち、転移細胞はこれに適応して初めて定着できる点が近年の再合成で前景化した。乳がん脳転移では O-GlcNAc 転移酵素 OGT が CDK5 経由で acetyl-CoA 合成酵素 ACSS2 の Ser267 をリン酸化して安定化し、ACSS2 が E2F1-SLC7A11 軸を介して鉄依存性細胞死 ferroptosis を抑制することで脳実質生存を担保する — p-ACSS2-S267 は 86 例の異種がん脳転移 TMA の約 94% で検出される pan-brain-metastasis バイオマーカー候補であり、脳透過性 ACSS2 阻害薬 AD-5584 が前臨床で腫瘍退縮と生存延長を示した (Young et al. CancerRes 2026)。肺腺がん脳転移では神経内分泌分泌タンパク VGF が ABHD12B の加水分解酵素活性を阻害して cardiolipin を保全し、mitochondrial fusion と酸化的リン酸化 (OXPHOS) への代謝シフトを駆動して脳内生存を支え、脳転移巣での高発現が独立予後不良因子となる (Wang et al. CancerRes 2026)。これらは免疫・関門軸とは独立に、BBB 透過性をもつ代謝酵素阻害薬という新しい治療軸が立ち上がりつつあることを示す。

がん種横断的差異と CNS-active 治療体系の確立: がん種横断的に共通するのは astrocyte-骨髄系軸による免疫抑制と BBB 透過性破綻だが、メラノーマ脳転移は ICI 感受性が高く、乳がん脳転移では免疫景観が予後を規定し (Jassowicz et al. CancerCell 2026)、NSCLC 脳転移は driver 依存的で CIN と空間的不均一性が強い (Tagore et al. NatMed 2025) という相違がある。CNS-active 薬剤は CSF/plasma ratio の階層 (Lorlatinib ≫ Osimertinib ≫ 1st-gen TKI) に基づき設計され、driver × generation 一致の物理化学的最適化が決定的に重要である。FLAURA で Osimertinib の頭蓋内 ORR 66% / CNS-PFS 延長、CROWN で Lorlatinib の CNS-PFS HR 0.06、Stage III EGFR+ では LAURA (Osimertinib consolidation) が確立し、無症候性小病変では次世代 TKI 先行・SRS deferral が主流となった一方、大型・症候性病変には早期局所治療が推奨される (Mavrikios et al. AnnOncol 2026)。Mavrikios らは driver subtype × CNS-active TKI × ADC (抗体薬物複合体 antibody-drug conjugate) × radiotherapy × IO の sequencing matrix を新しい標準枠組として提案し、ADC+SRT 併用での 2 年症候性 RN 率 8.5% など毒性管理を新たな課題として前景化した。Leptomeningeal disease は脈絡叢血管の permissive 化を機序とし依然予後不良で、5-HIAA-AHR 軸の標的化が新規予防戦略の候補となる (Huang et al. NatCancer 2026 / Leptomeningeal-metastasis)。

主要エンティティ

薬剤クラス (CNS-active 中心)

• EGFR-TKI — Osimertinib (3rd-gen), Lazertinib (CNS active, leptomeningeal で高用量試行)
• ALK-TKI — Alectinib (2nd-gen), Lorlatinib (3rd-gen, P-gp 非基質で BBB 完全カバー), Brigatinib
• ROS1-TKI — Entrectinib / Repotrectinib (baseline CNS active)
• RET-inhibitor — Selpercatinib / Pralsetinib (intracranial ORR 60–82%)
• NTRK-inhibitor — Larotrectinib / Entrectinib (CNS active)

関連遺伝子 (脳転移好発 driver)

• EGFR — CNS metastasis 好発、Osimertinib で抑制
• ALK — CNS 5-yr 再発率 60%+、世代別 ALK-TKI で抑制
• HER2 — 乳癌 brain met に Tucatinib、NSCLC HER2 mutant でも CNS active T-DXd

試験 (CNS efficacy 解析重視)

• ALEX — CNS PFS HR 0.16 (Alectinib)
• CROWN — 12-month CNS PFS 96% vs 18% (Lorlatinib)
• FLAURA — CNS PFS HR 0.48 (Osimertinib)
• AURA3 — CNS efficacy 詳細解析 (Wu JCO 2018)

(Phase B 拡張候補: Tucatinib / 脳転移サブグループ解析専用試験 / ANITA-1 等)

主要概念

• Pre-metastatic-niche — neural niche と PMN 形成の重なり、astrocyte/microglia reprogramming
• NETosis-cancer-metastasis — NET-mediated brain metastasis (CCDC25 軸の脳実質 / leptomeningeal 適用)
• Cancer-dormancy — 脳転移後 dormancy の long-term latency, late recurrence (5+ 年) の機序
• EMT — brain met 形成での mesenchymal shift、BBB 通過の運動性獲得

(Phase D 拡張候補: BBB/BTB permeability dynamics / astrocyte-tumor crosstalk / leptomeningeal seeding / neural-tumor synapse / reactive microglia in brain met / sensory-sympathetic axis)

Open Questions

• BBB/BTB 透過性・薬剤到達を症例ごとに予測するモデルが未確立で、CTC 由来の GPNMB-FTO-TJP1 m6A 軸 (Liu et al. CancerDiscov 2026) のような分子マーカーに基づく予測も依然経験則に依存し、CHI3L1・cluster 21 神経様状態・S100A9/RAGE・IFITM1 等の脳転移特異的 biomarker の臨床検証も未完である
• 脳転移特異的な immune cold の主因が IFNγ 非依存的な HLA-I APM 抑制 (Vilarino et al. MolCancer 2026) であるなら、APM 再活性化 (epigenetic 修飾 / ERBB4・PI3K 経路阻害併用) が ICI 抵抗性を解除できるかは未検証
• 予後良好な TRM 様細胞・TLS が脳で de novo 形成されるのか原発巣で前感作され転移するのか (Yuan et al. CancerCell 2026) が不明で、全身療法による拡張か局所再活性化かという治療戦略選択に直結する
• Neural-tumor synapse・sensory-sympathetic 軸 (Wei et al. Nature 2026) や astrocyte-STAT3 軸 (silibinin) を治療標的化する具体的薬剤戦略 (β遮断薬・VSN 標的除神経の re-purposing 含む) の前向き臨床検証が未着手
• 脳特異的代謝適応 — acetate-ACSS2-ferroptosis 耐性 (Young et al. CancerRes 2026) と VGF-OXPHOS シフト (Wang et al. CancerRes 2026) — を標的とする BBB 透過性阻害薬 (AD-5584 等) の臨床有効性と健常脳組織への代謝毒性の許容範囲は未検証
• Leptomeningeal disease の標準治療が未確立で、5-HIAA-AHR 軸・脈絡叢標的 (Huang et al. NatCancer 2026)・髄注療法・全身療法の最適統合が課題
• SRS/SRT と ICI・CNS-active TKI の併用 sequencing (先行 vs 同時 vs 後行) の最適タイミングと放射線壊死 (ADC+SRT 併用で 2 年症候性 RN 8.5% 等) のリスク管理は前向きエビデンス不足 (Mavrikios et al. AnnOncol 2026)

重要論文 Top 10

1. ★★★★★ Boire et al. NatRevCancer 2020 — 脳転移 biology の包括的 framework
2. ★★★★★ Guldner et al. Cell 2020 — CNS myeloid-CXCL10 軸による免疫抑制機構
3. ★★★★★ Biermann et al. Cell 2022 — ヒトメラノーマ脳転移 single-cell atlas
4. ★★★★★ Wei et al. Nature 2026 — 神経-免疫軸を介した全身性免疫抑制の発見
5. ★★★★ Tagore et al. NatMed 2025 — NSCLC 脳転移の空間的・single-cell 統合解析
6. ★★★★★ Achrol et al. NatRevDisPrimers 2019 — 脳転移 包括 review (疫学・病態・治療)
7. ★★★★ Quail et al. CancerCell 2017 — 脳腫瘍 microenvironment landscape — astrocyte/microglia/EC
8. ★★★★ Sanchez-Aguilera et al. CancerCell 2023 — Neural circuit ベースの脳転移サブタイプ分類
9. ★★★★ Faust et al. NatImmunol 2026 — Astrocyte-driven immunosuppression — IFN/STAT 軸
10. ★★★★ Huang et al. NatCancer 2026 — Leptomeningeal disease — choroid plexus permissive vasculature 機序

最新追加論文 Top 10

• Tian et al. NatBiomedEng 2026 — Basic-Extracellular vesicles
• Ma et al. JExtracellVesicles 2026 — Basic-Extracellular vesicles
• Routy et al. Science 2018 — Basic-Immunotherapy
• DiVizio et al. CancerRes 2009 — Basic-Extracellular vesicles
• Pegtel et al. ProcNatlAcadSciUSA 2010 — Basic-Extracellular vesicles
• Fuchs et al. ProcNatlAcadSciUSA 2010 — Basic-Neutrophil and myeloid cell
• Gabrilovich et al. NatRevImmunol 2012 — Basic-Neutrophil and myeloid cell
• De et al. JExtracellVesicles 2026 — Basic-Extracellular vesicles
• Wen et al. NatBiotechnol 2026 — Basic-Extracellular vesicles
• Zhu et al. JImmunotherCancer 2026 — Basic-Brain metastasis

全論文リスト (カテゴリ別、自動生成)

Basic-Brain metastasis

• Mavrikios et al. AnnOncol 2026 — Lung cancer brain metastases management at the dawn of personalized medicine are we ready to break the barriers
• Skribek et al. BrJCancer 2026 — The brain-lung immunotherapy prognostic (BLIP) score a novel robust tool for prognostication in non-small cell lung
• Jassowicz et al. CancerCell 2026 — Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes
• Yuan et al. CancerCell 2026 — Rethinking immune states in brain metastasis
• Ding et al. CancerDiscov 2026 — Glioblastoma-Secreted C1QL1 orchestrates Tumor microtube expansion and Neural synaptic pruning to drive malignant syn…
• Liu et al. CancerDiscov 2026 — GPNMB drives brain metastasis by sculpting a pathological endothelial-immune interactome
• Liu et al. CancerDiscov 2026 — Targeting the lipid metabolism proteins FASN and GPAM in alveolar type II cells decreases lung metastasis
• Wang et al. CancerRes 2026 — VGF-Mediated mitochondrial remodeling fuels lung adenocarcinoma brain metastasis
• Young et al. CancerRes 2026 — ACSS2 Suppresses Ferroptosis to Drive Breast Cancer Brain Metastasis
• Gao et al. Cell 2026 — Meningeal blood vessel blockage enhances anti-glioblastoma immunity
• Xu et al. Cell 2026 — Unbiased niche labeling maps immune-excluded niche in bone metastasis
• Yu et al. EBioMedicine 2026 — Tcf1+cd4+ t cells and microglia co-orchestrate tertiary lymphoid structures to enhance prognosis and immunotherapy in
• Cai et al. FrontImmunol 2026 — Mechanistic and functional characterization of NETsIL-17 as a therapeutic target in EMT and brain metastasis of lung
• Chen et al. FrontOncol 2026 — Stereotactic radiotherapy for brain metastases indications, dose fractionation, technological innovations, and evolving
• Jiang et al. FrontOncol 2026 — Advances in ommaya reservoir-based intrathecal therapy for leptomeningeal metastasis from non-small cell lung cancer a
• Weng et al. FrontOncol 2026 — Assessment of real-world surveillance strategies for patients undergoing systemic therapy for brain metastases
• Wang et al. IntJBiolSci 2026 — USP33 promotes lung adenocarcinoma brain metastasis by inhibiting the K48-linked ubiquitination and degradation of
• Maritan et al. JCIInsight 2026 — Distinct immune landscapes characterize highly versus minimally invasive brain metastases
• Lu et al. JClinOncol 2026 — Multicenter cohort study of original or substitute systemic therapy with or without brain radiotherapy for
• Kojundzic et al. JImmunotherCancer 2026 — Targeting B7-H3 in patients with metastatic triple-negative breast cancer and brain metastases an opportunity to revive
• Zhu et al. JImmunotherCancer 2026 — Spatial immune atlas of breast cancer brain metastasis reveals CD163
• Dee et al. JNatlCancerInst 2026 — Brain metastases among older people with cancer
• Vilarino et al. MolCancer 2026 — NSCLC brain metastases exhibit reduced HLA-I antigen presentation machinery and immune evasion independent of IFNgamma
• Huang et al. NatCancer 2026 — Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through
• Fox et al. NatCommun 2026 — Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of estrogen receptor-positive breast cancer brain
• Lin et al. NatCommun 2026 — Complex i protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases
• Faust et al. NatImmunol 2026 — Astrocyte-driven immunosuppression in the brain tumor microenvironment
• Wei et al. Nature 2026 — Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis
• Voglis et al. NeuroOncol 2026 — Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune 1
• Li et al. OncolLett 2026 — Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (…
• Yang et al. SciAdv 2026 — Glycerol-mediated nose-to-brain codelivery of anti-IL-17 and anti-CD73 antibodies enhances immunotherapy for melanoma
• Chafe et al. SciSignal 2026 — Emerging paradigms in the study of brain metastases
• Rodriguez-Baena et al. CancerCell 2025 — Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases
• Hill et al. NatCommun 2025 — Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
• Tagore et al. NatMed 2025 — Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases
• Kovacs et al. NatRevImmunol 2025 — Immune control of brain physiology
• Doglioni et al. Nature 2025 — Aspartate signalling drives lung metastasis via alternative translation
• Wang et al. STARProtoc 2025 — Protocol for generating brain metastatic tumor cells through repeated intracardiac injections in mice
• Dunbar et al. TrendsCancer 2025 — Regulation of metastatic organotropism
• Fu et al. CancerCell 2024 — Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade
• Liu et al. CancerPathogTher 2024 — Experimental models for cancer brain metastasis
• Jakab et al. NatCancer 2024 — Lung endothelium exploits susceptible tumor cell states to instruct metastatic latency
• Rabas et al. NatRevCancer 2024 — Cancer-induced systemic pre-conditioning of distant organs building a niche for metastatic cells
• Huang et al. CancerCell 2023 — CD44+ lung cancer stem cell-derived pericyte-like cells cause brain metastases through GPR124-enhanced
• Sanchez-Aguilera et al. CancerCell 2023 — Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits
• Huang et al. CellOncol(Dordr) 2023 — Involvement of ACACA (acetyl-CoA carboxylase alpha) in the lung pre-metastatic niche formation in breast cancer by
• She et al. EMBOJ 2023 — Immune surveillance of brain metastatic cancer cells is mediated by IFITM1
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• Monteiro et al. NatMed 2022 — Stratification of radiosensitive brain metastases based on an actionable S100A9RAGE resistance mechanism
• Satcher et al. NatRevCancer 2022 — Evolving cancer-niche interactions and therapeutic targets during bone metastasis
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Basic-Extracellular vesicles

• Jung et al. ACSSens 2026 — Wash-free digital detection of tumor extracellular vesicles via plasmonic droplet microfluidics
• Feng et al. AdvSci 2026 — S100A14 in tumor-derived evs targets PIAS3 to reprogram astrocytes and induce immunosuppressive microenvironment
• Schmidt et al. AmJPhysiolCellPhysiol 2026 — Extracellular vesicles in exhaled breath condensate as emerging biomarkers in lung cancer
• Dumontet et al. CancerCell 2026 — When more target antigen expression is less
• Fan et al. CancerCell 2026 — Cancer stem cells orchestrate immune evasion through extracellular vesicle-mediated non-canonical signaling pathways
• Hendrix et al. CancerCell 2026 — Extracellular vesicles whisperers of tumor immune evasion
• Hu et al. CancerCell 2026 — Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity
• Ji et al. CancerCell 2026 — T cell extracellular vesicles go nuclear to turn cold tumors hot
• Wang et al. CancerCell 2026 — Endocytic evasion confers resistance to antibody-drug conjugates therapy in cancer
• Xue et al. CancerCellInt 2026 — Tissue-derived extracellular vesicles comparing ts-EVs and te-EVs in extraction, characteristics and research trends
• Hudson et al. CancerLett 2026 — Human neural stem cell-derived extracellular vesicles improve cognitive function following glioma chemoradiation therapy
• Chayama et al. Cell 2026 — Physiological brain clearance architecture revealed by neuronal protein tracing
• Peng et al. CellMolBiolLett 2026 — Lactate-activated astrocytes promote NSCLC brain metastasis through extracellular vesicle-mediated miR-8085trim67elk1
• Zhang et al. CellRepMed 2026 — Artificial exosomes synergistically reshape sepsis immune homeostasis by modulating neutrophil fate and blocking
• Chen et al. FrontImmunol 2026 — Exosomal POSTN from cancer-associated fibroblasts drives progression of microinvasive lung adenocarcinoma insights from
• Pontis et al. JExpClinCancerRes 2026 — Circulating extracellular vesicles from early-stage lung cancer patients trigger endothelial activation to drive
• De et al. JExtracellVesicles 2026 — Characterizing the fate of anti-CS1 nanobody displaying extracellular vesicles in multiple myeloma
• Lee et al. JExtracellVesicles 2026 — Systemic propagation of STING signalling via generation of large extracellular vesicles
• Li et al. JExtracellVesicles 2026 — Exosomal oleic acid promotes lymphangiogenesis and nodal metastasis in cervical cancer via the AKTmTOR pathway
• Ma et al. JExtracellVesicles 2026 — Enterococcus faecalis extracellular vesicles deliver the bacterial GTPase obg to hijack mTOR signalling in
• Seo et al. JExtracellVesicles 2026 — Proteomic profiling of human extracellular vesicles reveals diagnostic biomarkers for colon adenocarcinoma
• Walther et al. JExtracellVesicles 2026 — Therapeutic poxviruses induce the secretion of immunostimulating and anti-tumoral extracellular vesicles
• Xie et al. JExtracellVesicles 2026 — Predictor a non-enzymatic catalytic cascade tool for in situ visualization of small extracellular vesicle surface
• Zhang et al. JExtracellVesicles 2026 — In situ engineered cascade-amplified drug-loaded vesicles for enhanced cancer stem cell therapy
• Du et al. JNanobiotechnology 2026 — Plant-derived nanovesicles the intelligent nanoplatforms for therapeutics and drug delivery
• Liu et al. JNanobiotechnology 2026 — Overcoming blood-brain barrier and chemoresistance in glioblastoma by angiopep-2-modified NK cell-derived extracellular
• Cai et al. MolCancer 2026 — Extracellular vesicles in solid tumors from tumor ecology to engineered therapeutics
• You et al. NatAging 2026 — Brain endothelial cell-derived extracellular vesicles (c-beevs) as a promising biomarker for brain vascular pathology
• Tian et al. NatBiomedEng 2026 — Skeletal-muscle-targeted non-viral delivery of full-length DMD mRNA for duchenne muscular dystrophy
• Wen et al. NatBiotechnol 2026 — Spatially resolved profiling of extracellular vesicles in tissues with spatial-EV-seq
• Goh et al. NatCommun 2026 — Sarcopenia promotes tumorigenesis by disrupting NOTCH-SDC2-regulated biogenesis of muscle-derived extracellular vesicles
• Shen et al. NatCommun 2026 — Co-enrichment of proteins in extracellular vesicles
• Liang et al. NatNeurosci 2026 — Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits
• Chaudhari et al. NatRevBioeng 2026 — The status of extracellular vesicles a drug carriers and therapeutics
• Ripoll et al. NatRevMolCellBiol 2026 — Biology and therapeutic potential of extracellular vesicle targeting and uptake
• Wei et al. NucleicAcidsRes 2026 — SVAtlas a comprehensive single extracellular vesicle omics resource
• Guo et al. SciAdv 2026 — Helper lipid-engineered extracellular vesicles enable PET imaging-guided pulmonary siRNA delivery to treat lung
• Stephens et al. BrJAnaesth 2025 — Human neutrophil-derived extracellular vesicles induce renal endothelial inflammation in critical illness an ex vivo
• Lucotti et al. Cell 2025 — Extracellular vesicles from the lung pro-thrombotic niche drive cancer-associated thrombosis and metastasis via
• Li et al. CellMetab 2025 — Liver-breast communication of adipocyte-oriented exosomes drives primary mammary cancer progression
• Xue et al. CellMetab 2025 — Extracellular vesicles from obese visceral adipose promote pancreatic cancer development and resistance to immune
• Tang et al. CellSignal 2025 — N2 neutrophils induce cell stemness reprogramming to promote gastric cancer progression via exosomal miRNAs
• Xie et al. IntImmunopharmacol 2025 — Neutrophil-derived exosomes promote sepsis-related multiple organ dysfunction through the induction of neutrophil
• Yang et al. JClinInvest 2025 — HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin beta3-containing
• Crescitelli et al. JExtracellVesicles 2025 — Recommendations for studying in situ extracellular vesicles from solid tissue
• Qiu et al. MolCancerRes 2025 — Insulin resistance increases TNBC aggressiveness and brain metastasis via adipocyte-derived exosomes
• Arya et al. NatCellBiol 2025 — Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation
• Son et al. NatCommun 2025 — Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes
• Yu et al. NatCommun 2025 — Defective neutrophil-derived exosomes facilitate macrophage activation through miR-122-5p in Behcet’s disease
• Greening et al. NatRevClinOncol 2025 — Clinical relevance of extracellular vesicles in cancer-therapeutic and diagnostic potential
• Richter et al. STARProtoc 2025 — Protocol for the isolation of human neutrophil-derived extracellular vesicles for characterization and functional
• Giudice et al. SciTranslMed 2025 — Target antigen-displaying extracellular vesicles boost CAR T cell efficacy in cell and mouse models of neuroblastoma
• Ma et al. SciTranslMed 2025 — Tumor extracellular vesicle-derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming
• Liu et al. ACSApplMaterInterfaces 2024 — Cell-specific impacts of surface coating composition on extracellular vesicle secretion
• Esmaeili et al. BiochemBiophysResCommun 2024 — Metabolically healthy unhealthy obesity and breast cancer
• Zhongyu et al. BiomedPharmacother 2024 — Review of pre-metastatic niches induced by osteosarcoma-derived extracellular vesicles in lung metastasis A potential
• Casanova-Salas et al. CancerCell 2024 — Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution
• Swanton et al. Cell 2024 — Embracing cancer complexity Hallmarks of systemic disease
• Tsering et al. CellDeathDis 2024 — Extracellular vesicle-associated DNA ten years since its discovery in human blood
• Deng et al. CellRep 2024 — Extracellular-vesicle-packaged S100A11 from osteosarcoma cells mediates lung premetastatic niche formation by
• Palmulli et al. NatCellBiol 2024 — CD63 sorts cholesterol into endosomes for storage and distribution via exosomes
• Gong et al. NatMater 2024 — Tumour-derived small extracellular vesicles act as a barrier to therapeutic nanoparticle delivery
• Arvanitaki et al. ProcNatlAcadSciUSA 2024 — Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage
• Dror et al. ResSq 2024 — Tumour-derived extracellular vesicle and particle reprogramming of interstitial macrophages in the lung pre-metastati…
• Bojmar et al. STARProtoc 2024 — Protocol for cross-platform characterization of human and murine extracellular vesicles and particles
• Ortmann et al. SciRep 2024 — Large extracellular vesicle (EV) and neutrophil extracellular trap (NET) interaction captured in vivo during systemic
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• Wight et al. AmJPhysiolCellPhysiol 2023 — V3 An enigmatic isoform of the proteoglycan versican
• Clancy et al. AnnuRevPathol 2023 — Tumor-derived extracellular vesicles multifunctional entities in the tumor microenvironment
• Jones et al. BMCBioinformatics 2023 — Tidyproteomics An open-source R package and data object for quantitative proteomics post analysis and visualization
• Patel et al. Bioengineering(Basel) 2023 — Extracellular vesicles as regulators of the extracellular matrix
• Ranathunge et al. BioinformAdv 2023 — promor A comprehensive R package for label-free proteomics data analysis and predictive modeling
• Tang et al. BrainRes 2023 — Activated neutrophil-derived exosomes contribute to blood-brain barrier damage and hemorrhagic transformation after
• Patras et al. CancerCell 2023 — Immune determinants of the pre-metastatic niche
• Garcia et al. CancerLett 2023 — Fernandez-Exosome-like systems Nanotechnology to overcome challenges for targeted cancer therapies
• Chhabra et al. Cell 2023 — Fibroblasts in cancer Unity in heterogeneity
• Kalluri et al. Cell 2023 — The role of extracellular vesicles in cancer
• Wang et al. CellMetab 2023 — Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment
• Cocozza et al. EMBOJ 2023 — Extracellular vesicles and co-isolated endogenous retroviruses from murine cancer cells differentially affect dendritic
• Asao et al. ExtracellVesiclesCircNuclAcids 2023 — Extracellular vesicles and particles as mediators of long-range communication in cancer connecting biological function
• Cun et al. GenomicsProteomicsBioinformatics 2023 — Specific regulation of m6A by SRSF7 promotes the progression of glioblastoma
• Ochkasova et al. IntJMolSci 2023 — Two edges in our knowledge on the functions of ribosomal proteins the revealed contributions of their regions to
• Mugoni et al. JExtracellBiol 2023 — Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the
• Blavier et al. JExtracellVesicles 2023 — The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory
• Sriwastva et al. JExtracellVesicles 2023 — An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth
• Su et al. JExtracellVesicles 2023 — Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis
• Frederickson et al. MolTher 2023 — Extracellular vesicles Expanding the landscape for next-generation delivery strategies in gene and cell therapy
• Radler et al. MolTher 2023 — Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
• Shin et al. NatMater 2023 — Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy
• Buzas et al. NatRevImmunol 2023 — The roles of extracellular vesicles in the immune system
• Dixson et al. NatRevMolCellBiol 2023 — Context-specific regulation of extracellular vesicle biogenesis and cargo selection
• Kozlov et al. NatRevMolCellBiol 2023 — Generation of nanoscopic membrane curvature for membrane trafficking
• Wang et al. Nature 2023 — Tumour extracellular vesicles and particles induce liver metabolic dysfunction
• Chung et al. ProcNatlAcadSciUSA 2023 — Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis
• Merlotti et al. SciImmunol 2023 — Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent
• Hu et al. SemCancerBiol 2023 — Tumor-derived nanoseeds condition the soil for metastatic organotropism
• Jeppesen et al. TrendsCellBiol 2023 — Extracellular vesicles and nanoparticles emerging complexities
• Shin et al. Biomaterials 2022 — Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles
• Wang et al. CancerImmunolImmunother 2022 — Tumor derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1 fibroblast and CCR8 Treg cell…
• Kudo et al. CellMetab 2022 — Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma
• Clancy et al. CellRep 2022 — Recruitment of DNA to tumor-derived microvesicles
• Amorim et al. Cells 2022 — Extracellular vesicles derived from MDA-MB-231 cells trigger neutrophils to a pro-tumor profile
• Moon et al. Cells 2022 — Exosome as a delivery vehicle for cancer therapy
• Doulabi et al. CommunBiol 2022 — Surface protein profiling of prostate-derived extracellular vesicles by mass spectrometry and proximity assays
• Lucotti et al. EMBOJ 2022 — Extracellular vesicles and particles impact the systemic landscape of cancer
• Leger et al. EMBORep 2022 — Functional platelet-derived mitochondria induce the release of human neutrophil microvesicles
• Ramos et al. FluidsBarriersCNS 2022 — Zaldivar-Extracellular vesicles through the blood-brain barrier a review
• Allen et al. FrontImmunol 2022 — Extracellular vesicles from A23187-treated neutrophils cause cGAS-STING-dependent IL-6 production by macrophages
• Aimaletdinov et al. IntJMolSci 2022 — Tracking of extracellular vesicles’ biodistribution new methods and approaches
• Breitwieser et al. IntJMolSci 2022 — Detailed characterization of small extracellular vesicles from different cell types based on tetraspanin composition by
• Glemain et al. JAutoimmun 2022 — Neutrophil-derived extracellular vesicles induce endothelial inflammation and damage through the transfer of miRNAs
• Almeida et al. JExtracellVesicles 2022 — Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with
• Jung et al. JExtracellVesicles 2022 — Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer
• Leary et al. JExtracellVesicles 2022 — Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes
• Liu et al. JExtracellVesicles 2022 — Extracellular vesicles from lung tissue drive bone marrow neutrophil recruitment in inflammation
• Yates et al. JExtracellVesicles 2022 — In sickness and in health the functional role of extracellular vesicles in physiology and pathology in vivo part I
• Yates et al. JExtracellVesicles 2022 — In sickness and in health the functional role of extracellular vesicles in physiology and pathology in vivo part II
• Guimaraes et al. JLeukocBiol 2022 — Bastos-Melanoma-derived extracellular vesicles skew neutrophils into a pro-tumor phenotype
• Han et al. MolCancer 2022 — Exosome biogenesis machinery, regulation, and therapeutic implications in cancer
• Arya et al. NatCellBiol 2022 — Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation
• El-Shennawy et al. NatCommun 2022 — Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
• Qi et al. NatCommun 2022 — Lin28B-high breast cancer cells promote immune suppression in the lung pre-metastatic niche via exosomes and support
• Wedge et al. NatCommun 2022 — Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy
• Xie et al. NatCommun 2022 — Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-beta type II receptor signaling
• Spackova et al. NatMethods 2022 — Label-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles
• Cheng et al. NatRevDrugDiscov 2022 — Therapeutically harnessing extracellular vesicles
• vanNiel et al. NatRevMolCellBiol 2022 — Challenges and directions in studying cell-cell communication by extracellular vesicles
• Bertolini et al. Oncogene 2022 — NFkappaB activation by hypoxic small extracellular vesicles drives oncogenic reprogramming in a breast cancer
• Tyagi et al. Oncogene 2022 — Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer
• Wang et al. ProcNatlAcadSciUSA 2022 — Tumor-polarized GPX3+ AT2 lung epithelial cells promote premetastatic niche formation
• Zhang et al. SciAdv 2022 — Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy
• Bao et al. TranslLungCancerRes 2022 — Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer
• Wang 2022 — Systemic regulation of metastatic disease by extracellular vesicles and particles
• Yu et al. AnnOncol 2021 — Exosome-based liquid biopsies in cancer opportunities and challenges
• Gurung et al. CellCommunSignal 2021 — The exosome journey from biogenesis to uptake and intracellular signalling
• Wu et al. CellDeathDis 2021 — TGFb1 mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p EPB41L5 axis to p…
• Crewe et al. CellMetab 2021 — Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes
• Isaac et al. CellMetab 2021 — Exosomes as mediators of intercellular crosstalk in metabolism
• Morrissey et al. CellMetab 2021 — Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant
• Fitzgerald et al. CellRepMethods 2021 — A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
• Mosbach et al. Cells 2021 — Molecular determinants for RNA release into extracellular vesicles
• Ma et al. CurrProtoc 2021 — Characterization and functional analysis of tumor-derived microparticles
• Matsui et al. EMBORep 2021 — ALIX and ceramide differentially control polarized small extracellular vesicle release from epithelial cells
• Lucchetti et al. EurRespirJ 2021 — Detection and characterisation of extracellular vesicles in exhaled breath condensate and sputum of COPD and severe
• Clancy et al. FASEBBioadv 2021 — The ins and outs of microvesicles
• Jin et al. FrontCellDevBiol 2021 — Rab GTPases Central coordinators of membrane trafficking in cancer
• Esposti et al. IntJMolSci 2021 — Exosomes from plasma of neuroblastoma patients contain doublestranded DNA reflecting the muational status of parental…
• Gorji-Bahri et al. JCellBiochem 2021 — RAB5A is associated with genes involved in exosome secretion integration of bioinformatics analysis and experimental
• Kadota et al. JExtracellVesicles 2021 — Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of
• Veerman et al. JExtracellVesicles 2021 — Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical
• Xiao et al. MolCancerRes 2021 — Exosomal delivery of FTO confers gefitinib resistance to recipient cells through ABCC10 regulation in an m6a-dependent
• Aday et al. MolTher 2021 — Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in
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• Clancy et al. NatCellBiol 2021 — Profiling and promise of supermeres
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• Zhang et al. NatCellBiol 2021 — Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
• An et al. NatCommun 2021 — An active tethering mechanism controls the fate of vesicles
• Lima et al. NatCommun 2021 — Tumor microenvironmental cytokines bound to cancer exosomes determine uptake by cytokine receptor-expressing cells and
• Mathieu et al. NatCommun 2021 — Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9
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