Ptgs2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy pharmacological inhibition of PTGS2 was similarly effective. We found that PTGS2, the gene encoding cyclooxygenase-2, lies downstream of EPHA2 signaling through TGFβ and is associated with poor patient survival. Epha2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy. From human tumors, we identified EPHA2 as a candidate tumor intrinsic driver of immunosuppression. We conducted an unbiased approach to identify tumor-intrinsic mechanisms shaping the immune tumor microenvironment(TME), focusing on pancreatic adenocarcinoma because it is refractory to immunotherapy and excludes T cells from the TME. WhileT cell abundance is essential for tumor responsiveness to immunotherapy, factors that define the T cell inflamed tumor microenvironment are not fully understood. Resistance to immunotherapy is one of the biggest problems of current oncotherapeutics.
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