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In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.
This open question asks what actually holds T cells at the tumour border: in immune-excluded tumours the immune cells are present but cannot get in, and knowing the dominant barrier would open the gate. Fibroblasts, matrix, abnormal vessels, CXCL12 gradients and myeloid cells are all implicated, yet TGF-β-directed drugs failed as monotherapy, suggesting redundancy or wrong patient selection. The hypothesis is that a few stromal programmes, classifiable by Single-cell & spatial profiling, drive Immune exclusion, so matching the agent (TGF-β, FAP, CXCR4 or VEGF) to the programme converts excluded tumours into inflamed ones. The test is a biomarker-stratified window trial with PD-1 blockade, and the idea links to FAPI PET and Hot vs cold tumours.
Shares Gustave Roussy, PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center, PD-1 and the tags mechanism, open-question.
Shares Gustave Roussy, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1 and the tags mechanism, open-question.
Shares Single-cell & spatial profiling, Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.