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TodayOct 16Fri
  1. biopharmadive.com49

    Belgian startup revives Galapagos CAR-T research

    Lakefront Biotherapeutics, formerly Galapagos, has sold its cell therapy programmes to Belgian startup Armed Cell Therapeutics for 8 million euros up front, with up to $230 million more in future payments. The deal covers two armed CAR-T therapies nearing human testing in non-Hodkin lymphoma and small cell lung cancer, plus three undisclosed preclinical projects. Armed Cell named Willemijn Kremer, a former Galapagos cell therapy executive, as CEO, replacing interim CEO Paul Stoffels.

    Why it matters: Revives shelved CAR-T programmes under a new company after Galapagos wound down its cell therapy research.

Oct 15Thu
  1. ema.europa.eu90

    EMA recommends authorisation of Rasonque for metastatic pancreatic cancer

    EMA's CHMP has recommended EU marketing authorisation for Revolution Medicines' Rasonque (daraxonrasib), an oral RAS inhibitor for adults with metastatic pancreatic adenocarcinoma previously treated at least once. In a 500-patient phase 3 study, median overall survival was 12.4 months versus 6.7 with chemotherapy, and median progression-free survival 7.2 versus 3.6 months. The European Commission will now fast-track its decision, with pricing left to Member States.

    Why it matters: CHMP backing via a phased review under 150 days sets precedent for faster EU assessments of priority cancer medicines.

  2. biorxiv.org49

    Pervasive expression of early embryonic programs in cancer has stage-dependent survival impact

    Early embryonic gene expression programs are widespread in human tumours, and transcriptional similarity to distinct preimplantation stages independently predicts overall survival beyond age, sex, mutational status and molecular subtype. Similarity to zygote and 2-cell embryo stages predicted improved survival, driven in kidney cancer by stromal and immune cells, while trophectoderm-associated programs in tumour cells predicted worse survival in breast cancer and melanoma and were linked to MYBL2 and FOXM1 dependencies.

  3. biorxiv.org42

    Tobacco Carcinogen Induces Persistent DNA Damage and Homologous Recombination Dysregulation in Pancreatic Ductal Carcinogenesis

    The tobacco carcinogen NNK produces a biphasic DNA damage response in human pancreatic ductal epithelial cells: 5 days of exposure induced double-strand breaks with ATM-γH2AX activation and RAD51/BRCA2 recruitment, while 50 days caused persistent damage signaling, upregulation of HR genes (RAD51, BRCA1, BRCA2, FANCD2, PLK1), altered RAD51 localization, and chromosomal instability. In human PDAC tissue microarrays and TCGA-PAAD data, increased γH2AX correlated with tumor progression and poor overall survival, and elevated RAD51 with adverse outcomes, positioning γH2AX as a candidate prognostic biomarker in tobacco-associated PDAC.

  5. biorxiv.org61

    A microbiota-driven neuroepithelial feed-forward circuit drives gastroesophageal junction tumorigenesis

    Bile acid remodeling enriches the oral commensal Prevotella melaninogenica at the gastroesophageal junction, where bacterial succinate activates vagal sensory neurons and SUCNR1-expressing tuft cells. Tuft cells release 15-d-PGJ2 to sensitize sensory neurons, while neuronal CGRP drives expansion and tuft-cell differentiation of neuro-responsive epithelial progenitors through RAMP1, forming a self-reinforcing microbiota-neuron-epithelium circuit that promotes dysplastic progression. Genetic or pharmacological disruption of the circuit, including with the approved CGRP antagonist rimegepant, suppresses tumor development.

  6. biorxiv.org48

    scIRES-seq reveals multimodal molecular heterogeneity in CTCs from small cell cervical cancer

    scIRES-seq, a new single-cell framework linking immunophenotype, genetic variation, DNA methylation and gene expression, was coupled to real-time imaging spectral flow cytometry and applied to circulating tumor cells from a patient with metastatic cervical small cell neuroendocrine carcinoma. Tumor-matched copy-number alterations and targeted somatic variants established CTC identity, and methylation profiles matched metastatic tissue. Genetic and methylation analyses identified two CTC subpopulations that transcriptomes alone did not distinguish, showing the value of multi-omics profiling of rare cells.

    Why it matters: It offers a working method to integrate identification and multi-omic characterization of rare circulating tumor cells.

  7. medicalxpress.com53

    Expanded genetic testing and early transplant referrals anchor new myelofibrosis care recommendations

    The American Society of Hematology has issued 10 evidence-based recommendations for managing myelofibrosis, a rare blood cancer affecting up to six per 100,000 people, published in Blood Advances. The guidelines call for extended molecular testing at diagnosis, early transplant consultation for higher-risk patients responding to JAK inhibitors, appropriate JAK inhibitor use by risk level, anemia management strategies, and low-dose aspirin for patients with the JAK2 V617F mutation. Panel chair Brady Stein says the panel hopes the questions posed will set a future research agenda on treatment prediction, anemia and transplant timing.

    Why it matters: First ASH guidelines covering myelofibrosis care decisions from testing to transplant will shape clinical practice in a rare cancer.

  8. doi.org51

    Structural and Mechanistic Insights Into GSDME Pore Formation and Functional Regulation

    Cryo-EM structures of gasdermin E pores, with oligomeric stoichiometries ranging from 23 to 29 protomers, expose how pore assembly works. Mutagenesis, liposome leakage assays and cancer-associated mutation analysis identified residues governing membrane binding, shallow membrane insertion and oligomerization via three interfaces, while molecular dynamics simulations showed anionic TMCL2 recruited by basic residues to aid membrane penetration. The work supports a stepwise, time-dependent mechanism of GSDME pore assembly.

  9. doi.org41

    Dynamic changes of claudin 18.2 expression after systemic therapy in gastric and esophagogastric junction cancer

    Claudin 18.2 (CLDN18.2) expression in advanced gastric/esophagogastric junction adenocarcinoma changes frequently during systemic therapy. In paired samples from 155 patients, positivity rose from 54 (34.84%) before treatment to 61 (39.35%) after (p < .001); overall, 131 patients (84.52%) showed altered expression. Conversion rates did not differ between chemotherapy alone and chemotherapy plus immunotherapy, supporting CLDN18.2 reassessment before targeted therapy.

  10. Nat Biotechnol69

    Engineering bispecific exosome activators of T cells to target immune checkpoint inhibitor-resistant metastatic melanoma.

    An inhalable exosome system called BEAT co-displays PD-1 and FZD8 in a uniform 1:1 ratio to block PD-L1 and Wnt7b, overexpressed in immune checkpoint inhibitor-resistant melanoma. BEAT recruited and activated CD8+ T cells, reprogramming the tumor microenvironment and producing robust antitumor activity in mouse models of lung metastases, outperforming a linked dual antibody against PD-L1 and Wnt7b in vivo.

  11. Sci Adv46

    An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy.

    The ROCCIA mouse, a quintuple-mutant immunocompetent model, develops multifluorescent osteosarcoma tumors that allow labeled cell populations to be traced in tumors and in circulation, with postnatal inactivation of p53 and Rb1 resembling human OS development. Using it, Osx-expressing fluorescent tumor cells were shown to appear in circulation upon OS development and to predominate in lung metastases, marking a potential therapy target. The model's immune microenvironment mimics the human OS microenvironment.

  12. biopharmadive.com61

    Iambic, an AI drug discovery specialist, banks $150M in an IPO

    Iambic Therapeutics, an AI drug discovery startup, raised $150 million in an IPO, selling close to 9.4 million shares at $16 each and trading on the Nasdaq from Thursday under the ticker "IAM." The company has drawn $462 million in private funding since 2019 and will use the proceeds to advance its first drug, IAM1363, an oral tyrosine kinase inhibitor for HER2-positive solid tumors that showed anti-tumor activity and encouraging safety in a Phase 1 study, with a registrational trial possibly beginning in 2027. Behind it are IAM217, targeting KIF18A in ovarian and triple-negative breast cancers, and a CDK2/CDK4-targeting prospect, both potentially entering testing next year.

    Why it matters: The offering adds to a wave of AI drug discovery startups testing whether public investors will back the technology.

  13. medrxiv.org40

    Choroid plexus asymmetry on routine MRI as an imaging signature of breast cancer brain metastasis

    Choroid plexus asymmetry on routine contrast-enhanced brain MRI is associated with breast cancer brain metastasis. In 1,000 women with breast cancer, 190 with brain metastasis, a deep-learning-derived Choroid Plexus Asymmetry Index was elevated in metastasis cases (median 0.088 vs 0.059; adjusted OR 1.58 per +1 SD, 95% CI 1.32-1.88), independent of peripheral inflammation markers, histological grade, tumour laterality and metastasis side. Total choroid plexus volume did not differ between groups, pointing to asymmetry rather than size as the relevant signature.

  14. biorxiv.org49

    AMPK Signalling Rewires WWP1 mediated RUNX1 Ubiquitination in CML Progression

    The E3 ubiquitin ligase WWP1 binds the PPxY motif of RUNX1 and catalyzes K63-linked polyubiquitination that stabilizes the protein and drives chronic myeloid leukemia cell growth. AMPK phosphorylates WWP1 at Thr692, sending it to lysosomal degradation, and also phosphorylates RUNX1 to curb its leukemogenic activity. Metformin activated this AMPK-WWP1-RUNX1 axis in leukemia cell lines, primary CML patient-derived cells, and xenograft tumors, pointing to WWP1 as a therapeutic vulnerability.

  15. biorxiv.org40

    A Multi-Kinase Inhibitor Screen Identifies mTOR Signaling as a Vulnerability in Advanced Prostate Cancer.

    Loss of the receptor tyrosine kinase AXL is linked to treatment resistance, aggressive phenotypes, and shorter overall survival in prostate cancer. Screening isogenic CRISPR-generated AXL-knockout cells against 1,814 kinase inhibitors identified Torin-2, which showed an ~18-fold lower IC50 in AXL-knockout than AXL-wildtype cells. PRISM/DepMap analysis confirmed a selective vulnerability to PI3K/AKT/mTOR pathway inhibition, pointing to mTOR inhibition as a therapeutic strategy for AXL-deficient prostate cancer.

  16. biorxiv.org42

    Spatial Tumour Tissue Distribution Dynamics of a Bicycle Peptide-MMAE Toxin Conjugate Profiled by Targeted Mass Spectrometry

    Laser capture microdissection coupled to targeted LC-PRM mass spectrometry maps the spatial distribution of MMAE released from the NECTIN-4-binding Bicycle Drug Conjugate zelenectide pevedotin (BT8009) at sub-tissue resolution in mice. The method showed progressive accumulation and sustained retention of MMAE in tumour tissues over 24 h, while levels in plasma, liver and muscle declined after early exposure, and revealed heterogeneous MMAE distribution between tumour cell-rich and stroma-rich regions with distinct temporal patterns.

  17. nature.com64

    Divergent genomic evolution in astrocytomas and oligodendrogliomas

    Astrocytomas and oligodendrogliomas develop treatment resistance through different genomic routes, longitudinal analyses of patient tumours show. Astrocytomas accumulate copy-number alterations and markers of chromosomal instability, whereas oligodendrogliomas acquire new driver mutations. The finding separates the two tumour types by evolutionary mechanism rather than by histology alone.

Oct 14Wed
  1. fda.gov91

    FDA Approves First Treatment for Certain People With BCG-Unresponsive Bladder Cancer

    The FDA expanded approval of Anktiva (nogapendekin alfa inbakicept-pmln), given with BCG, to adults with BCG-unresponsive, high-grade papillary-only non-muscle invasive bladder cancer, the first FDA-approved treatment for that disease. The decision relied on evidence from Anktiva's earlier approval for carcinoma in situ, where a trial showed a majority of adults achieved a complete response and many maintained it for at least 12 months. The FDA is finalizing draft guidance to let developers use CIS study evidence for papillary-only NMIBC approvals.

    Why it matters: FDA extends Anktiva to BCG-unresponsive papillary-only NMIBC and sets a precedent for cross-indication evidence use.

  2. fda.gov76

    FDA approves an expanded indication for nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer

    On October 14, 2026, the FDA expanded approval of nogapendekin alfa inbakicept-pmln (Anktiva, Altor BioScience, an ImmunityBio subsidiary) with BCG to cover adults with BCG-unresponsive non-muscle invasive bladder cancer with high-grade papillary-only tumors, beyond the prior indication limited to carcinoma in situ. The agency extrapolated efficacy from Cohort A of QUILT-3.032, a single-arm trial of 77 patients, which showed a complete response rate of 62%. The recommended dose is 400 mcg intravesically with BCG weekly for 6 weeks induction, followed by maintenance for up to 37 months.

  3. Mol Cell65

    A feedback mechanism of m6A via PARP1-mediated ADP ribosylation of METTL3/METTL14.

    The m6A reader IGF2BPs recruits PARP1 to m6A-modified RNAs and stimulates its activity, leading to ADP ribosylation of the m6A writer METTL3/METTL14, which impairs its RNA-binding capability and reduces m6A deposition in human cell lines. This "read-orchestrate-write" negative feedback loop expands the regulatory paradigm of m6A methylation beyond the writer/eraser/reader system. Combining PARP inhibitor therapy with inhibition of IGF2BP2 or METTL3 produced synergistic anti-tumor effects.

  4. Mol Cell68

    Transposable element splicing reveals a tumor-enriched class of gene-independent transcripts.

    A pan-cancer analysis defines TEtrans, a splice-resolved class of transposable element-derived transcripts that are tumor-enriched and gene-independent. An endogenous retrovirus-derived TEtrans promotes colorectal cancer growth by enhancing topoisomerase I-mediated DNA relaxation, and a subset encodes shared tumor antigens that elicit cytotoxic T cell responses, with a murine TEtrans-like transcript mediating antigen-dependent tumor control in vivo. The work adds spliced TE transcripts to the roster of oncogenic drivers and actionable tumor antigens.

  5. Nat Biotechnol82

    In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles.

    Ligand-directed lipid nanoparticles (NtLNPs) carrying mRNA transfected up to ~80% of NK cells in vivo in mice with minimal off-target effects, generating CAR NK cells without ex vivo engineering. CD19-targeted CAR NKs completely depleted circulating B cells in healthy mice, CD3-targeted CAR NKs eliminated nearly all autoreactive T cells in autoimmune hepatitis, and NKG2A-targeting versions improved solid tumor efficacy. Human-optimized NtLNPs produced CAR NK cells that regressed two humanized hematologic malignancy models. The work replaces viral, ex vivo CAR manufacturing with a modular in vivo mRNA delivery platform.

    Why it matters: It shows nonviral in vivo CAR NK generation, a route around ex vivo viral engineering of cell therapies.

  6. biorxiv.org52

    Co-targeting KRAS and BCL-2 induces pyroptosis and antitumor tertiary lymphoid structures

    Co-targeting KRAS and BCL-2 synergistically triggers GSDME-mediated pyroptosis in KRAS G12D-mutant lung tumors, which are metabolically vulnerable through weakened HK1 interaction and reduced spare respiratory capacity compared with G12C. The combination induces functional tertiary lymphoid structures in vivo, and depletion experiments show the antitumor efficacy depends on B cells. It also drives membrane attack complex deposition in situ and elicits memory antitumor responses.

  7. biorxiv.org52

    Microglia-derived Small Extracellular Vesicles Promote Bone Marrow Monocyte Expansion and Recruitment in Glioblastoma.

    Tumor-associated microglia in glioblastoma release small extracellular vesicles that traffic to the bone marrow, where they selectively target monocytes and their progenitors. Internalization of these vesicles activates MAPK signaling and inflammatory transcriptional programs, driving differentiation and expansion of inflammatory monocytes that are then recruited into the tumor microenvironment. The work identifies a communication route between the glioblastoma TME and the peripheral immune system that helps establish the immunosuppressive TME driving GBM progression.

  8. biorxiv.org52

    Trp53 heterozygosity defines novel states impacting tumor plasticity and progression in Kras-initiated non-small cell lung cancer

    Trp53 single-allele loss expands transcriptional plasticity and increases genomic instability relative to complete Trp53 loss in KrasG12D-driven murine lung tumors, while K and KP+/- mice live longer than KP mice, matching clinical survival patterns. Murine KP+/- signatures and copy-number profiles appear in human NSCLC datasets, and two signatures correlate with better and worse patient survival, respectively. TP53 heterozygosity therefore defines a distinct genomic landscape that should inform therapeutic strategy in KRAS-mutant lung cancer.

  9. biorxiv.org48

    Oncogenic ETS factors expressed from fusion genes utilize EWSR1 to associate with the paraspeckle and regulate transcription.

    Oncogenic ETS fusion proteins ERG and EWSR1::FLI1 associate with the paraspeckle scaffold long non-coding RNA NEAT1_2, linking them to this EWSR1-containing nuclear organelle. Disrupting paraspeckles in prostate cancer and Ewing sarcoma cell lines disrupted oncogenic phenotypes and, in Ewing sarcoma cells, produced transcriptional profiles similar to loss of EWSR1::FLI1. The work identifies the paraspeckle as a transcriptional regulator and potential drug target in ETS fusion cancers.

  10. biorxiv.org45

    A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors

    A tiered precision oncology framework combining deep whole-genome sequencing, single-cell RNA sequencing, and ex vivo functional drug screening was applied to 17 children with malignant CNS tumors. Functional screening gave every patient at least one high-confidence targeted-therapy or chemotherapy nomination, single-cell RNA sequencing found an average of 37 druggable gene targets per patient, and high-confidence targeted-therapy recommendations rose fourfold. Functional classifications matched outcomes in 8 of 10 evaluable cases.

  11. biorxiv.org50

    Biomarker-driven and gene-enhanced viral therapy for malignant peripheral nerve sheath tumor

    Loss of the PRC2 histone mark H3K27me3, common in high-grade MPNST, sensitizes tumors to the oncolytic HSV G47Δ, but also triggers a compensatory integrated stress response that blunts viral protein translation. Engineers built G47Δ² with tumor-regulated ICP34.5 expression (BIRC5-driven), limiting daily xenograft tumor-volume growth to 0.6% (95% CI -2.9–4.2%) versus 8.3% for G47Δ² and 22.5% for controls, though murine gastrointestinal toxicity reduced event-free survival.

  12. biorxiv.org40

    Predicting resistance to synthetic lethal therapies in cancer

    Resistance to synthetic lethal cancer therapies can be predicted from molecular network features. A random forest model combining protein-protein interaction, co-expression and essentiality data, trained on CRISPR-Cas9 resistance screens across ten SL biomarker-target pairs, achieved a mean AUROC of 0.72 under leave-one-SL-pair-out validation (range 0.57-0.91) and independently predicted resistance to the MTAP-PRMT5 and ATM-ATR therapies now in trials. The work gives a computational way to anticipate resistance mechanisms before they emerge.

  13. Nat Med69

    A health-system-scale, episode-resolved multimodal atlas of cancer cachexia.

    Longitudinal clinicogenomic data from 52,236 patients with cancer profiled by MSK-IMPACT (2010-2024) show that cachectic weight loss episodes cluster near disease progression, worsen outcomes across nearly all cancer types, and carry a consistent serologic signature of lower albumin and hemoglobin with higher liver enzymes. Tumor genotypes including TP53 mutation were linked to more frequent episode onset. A model predicting impending cachectic weight loss in lung, colorectal and prostate cancer was validated in an external Dana-Farber cohort of 5,785 patients.

    Why it matters: It shows routine clinicogenomic data can identify cachexia drivers and predict weight loss risk at health-system scale.

  14. nature.com62

    Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial

    Adding the PARP inhibitor talazoparib to enzalutamide improved prostate-specific antigen response in patients with high-volume metastatic hormone-sensitive prostate cancer in the randomized phase 2 ZZ-FIRST trial. Spatial transcriptomic analysis of paired biopsies showed that androgen receptor inhibition suppresses homologous recombination repair-related programs, and this suppression correlated with proliferation arrest rather than functional HRR deficiency.

    Why it matters: Links AR inhibition to HRR program suppression, giving a mechanistic basis for combining PARP inhibition with androgen receptor inhibitors.

  15. nature.com50

    Personalized neoantigen-targeting cancer vaccines in ovarian cancer: a phase 1 trial

    Personalized neoantigen vaccines combined with PD-1 blockade were feasible in patients with high-grade serous ovarian cancer in a phase 1 trial. Many patients mounted tumor-specific immune responses. Cell-free DNA analysis identified putative resistance mechanisms related to antigen presentation. The trial establishes feasibility of this approach in ovarian cancer and points to antigen presentation as a resistance pathway.

  16. biocentury.com46

    Duracyte: Turning the patient into the bioreactor

    Duracyte, a Rice University spinout based in Houston, is developing subcutaneous implants of engineered human cells that continuously secrete biologics in the body for up to a year, with the aim of replacing repeated infusions and injections. The work has drawn roughly $120 million in non-dilutive funding. The company plans to start its first clinical trial in the first half of next year, testing an implant that produces the checkpoint inhibitor ipilimumab in patients with peritoneal cancer.

  17. medicalxpress.com46

    Long-term viral hepatitis control and changing patterns of liver cancer mortality in Japan

    A Hiroshima University review published in The Lancet Regional Health-Western Pacific finds that decades of national viral hepatitis control in Japan cut HBV and HCV prevalence sharply and reduced hepatocellular carcinoma mortality. HBsAg prevalence among first-time blood donors fell from 0.63% in 1995-2000 to 0.13% in 2017-2021, and the share of HCC deaths from nonviral causes rose from 6.8% in 1992 to 56.0% in 2019. The authors identify remaining gaps, including hepatitis in PWID, MSM, migrant and incarcerated populations, as Japan works toward the WHO 2030 elimination targets, and offer transferable lessons for other countries.

  18. medicalxpress.com57

    WHO experts recommend HPV shot for girls aged 4–8

    WHO's Strategic Advisory Group of Experts on Immunisation (SAGE) has recommended that countries consider routine HPV vaccination for girls as young as 4 if it boosts uptake, after confirming a single-dose schedule for girls aged 9 to 14 as the most efficient route to the 90% coverage target. Global HPV vaccine coverage stands at 33% across 165 introducing countries, while more than 95 million girls had been vaccinated by the end of 2025. SAGE also set priority groups for expanding single-dose vaccination: catch-up for women up to 25, then up to 30, routine vaccination of boys aged 9 to 14, and catch-up for males up to 20.

    Why it matters: SAGE guidance shapes national HPV vaccination policy as coverage remains far below the 90% target.

  19. medrxiv.org41

    MRI Biomarkers for Brain Metastases in Lung Cancer Using Machine Learning

    MRI-derived radiomic features improved prognostic stratification beyond clinical variables in 103 patients with brain metastases from lung cancer. The combined clinical-imaging DeepSurv model reached a concordance index of 0.728 for overall survival, and risk groups separated median overall survival at 26.7 versus 9.1 months. Imaging-only high-risk patients were less likely to have tumor-infiltrating lymphocytes and PD-L1 expression of at least 50%, linking the biomarkers to the tumor immune microenvironment.

  20. Sci Adv59

    Citron kinase activity controls alternative splicing events that drive prostate cancer growth.

    Citron (CIT) kinase drives prostate cancer growth by phosphorylating the RNA splicing regulator THRAP3, controlling its binding to pre-messenger RNA targets and producing transcripts that stimulate growth of prostate cancer cell lines, xenografts, patient-derived organoids, and PDX-derived organoids. An antisense oligonucleotide blocking THRAP3 recruitment to a CIT-dependent RNA binding site prevented production of these transcripts and inhibited growth of cell lines and PDX-derived organoids across prostate cancer stages and lineages, but not of benign cells. The work identifies CIT-mediated alternative splicing as a therapeutic strategy in treatment-resistant prostate cancer.

    Why it matters: It offers an indirect way to hit CIT kinase, for which no selective inhibitors exist, via a splicing antisense oligonucleotide.

  21. biorxiv.org57

    An RFX-driven ciliogenic cell state defines ex vivo FGFR-inhibitor sensitivity in colorectal cancer

    An RFX-driven ciliogenic cell state marked by upregulation of cilia-related genes predicts selective sensitivity to the FGFR inhibitor erdafitinib in colorectal cancer. Image-based ex vivo drug profiling with matched transcriptomics of 127 patient biopsies linked the signature to poor progression-free survival (hazard ratio 2.28; adjusted p=0.0098), even in early-stage disease, and knockdown of RFX2 and RFX3 attenuated erdafitinib sensitivity. The work offers a patient-stratified route to FGFR inhibition beyond current CRC treatment paradigms.

  22. biorxiv.org47

    Tumour-derived factors prime microglia for immune checkpoint-mediated T-cell regulation

    Soluble tumour-derived factors, not direct tumour contact, drive early microglial activation: quantitative proteomics showed extensive remodelling of the microglial proteome after exposure to tumour-conditioned media, with coordinated upregulation of MHC-I, PD-L1 and Galectin-9. Flow cytometry in murine and human cell models confirmed increased PD-L1 and MHC-I, and these microglia induced PD-1 and TIM-3 on cocultured T-cells. Single-cell RNA sequencing datasets from brain tumour patients recapitulate the same immune-regulatory program.

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