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Preprint WatchMildSeptember 25th, 2026

Radiation therapy synergizes with mRNA vaccination to overcome microglia-mediated suppression of dendritic cell migration and T cell priming in glioblastoma

Wisdom AJ, Rogers ZJ, Chatterjee F, Cui Y, Garcia-Rivera L, Temple H, Abdelfattah NS, Coombs T, Van R, Tafuri Del Vecchio C, So HK, Heim T, Wolczanski G, Mount CW, Butty V, Levine SS, Cormier K, Love JC, Kaech SM, Jacks T, White F, Spranger S.

Microglia-derived GAS6 and PROS1 signalling through AXL on dendritic cells suppresses dendritic cell activation and migration to tumour-draining lymph nodes, and pharmacological AXL inhibition restores dendritic cell migration and anti-tumour immunity.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

Wisdom and colleagues place AXL on dendritic cells rather than on tumour cells, reporting that microglia-derived GAS6 and PROS1 signalling through AXL blocks dendritic cell migration to tumour-draining lymph nodes in glioblastoma, and that pharmacological AXL inhibition restores it. That is a different therapeutic rationale from the one AXL programmes have generally carried into the clinic. The single matching entry, bemcentinib-axl-lung-adenocarcinoma-phase1b2-supply-termination, records an AXL inhibitor programme in advanced lung adenocarcinoma stopped for strategic reasons rather than for lack of effect, so the graph holds no evidence against AXL efficacy. The flag is mild and mostly forward-looking, since an immune-compartment rationale would need a different trial design, a different tumour type and a dendritic cell pharmacodynamic readout than the tumour-intrinsic programmes that came before.

Abstract excerpt

Glioblastomas (GBMs) are uniformly fatal brain tumors resistant to immunotherapy, yet the mechanisms driving immune dysfunction remain poorly understood. Here we identify a tissue-specific mechanism of dendritic cell (DC) dysfunction contributing to GBM immune evasion. We demonstrate that while systemic immunity depends on type 1 conventional DCs (cDC1s), GBMs preferentially accumulate cDC2s with impaired antigen-presenting capacity. Further, microglia-derived GAS6 and PROS1 signaling through the AXL receptor on DCs suppresses DC activation and, critically, migration to tumor-draining lymph nodes. Pharmacologic AXL inhibition enhances DC migration and consequently anti-tumor immunity. Importantly, radiation therapy activates cDC1-mediated endogenous immune responses, which synergizes with mRNA vaccination to promote complete and durable immune-mediated tumor regression. These findings establish DC-mediated immunity as a therapeutic target in brain tumors and reveal a synergistic mechanism for combining radiation with personalized cancer vaccines.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.