157 The tumor microenvironment limits the development and persistence of tissue-resident memory T cells

Tissue-resident memory T (TRM) cells have emerged as key players and potential immunotherapeutic targets in antitumor immunity. However, the study of TRM within TME has been hampered by a lack adequate tumor models. Cell lines injected subcutaneously do not contain same biological cues tumors arising from dermis epidermis, while most other models known tumor-specific antigen to track immune responses. We addressed these two issues modifying Braf/PTEN model melanoma express OVA (abbreviated BPO). In this novel model, we observe robust endogenous tumor-antigen specific response against measured IFN-γ ELISPOT, pentamer staining, adoptive transfer OT-I cells. contrast subcutaneous cell found significantly more CD8 TILs co-expressing CD103 CD69 autochthonous BPO (22.3±2.4 vs 2.5±0.27 SEM). Interestingly, CD103+ CD8+ expressed less PD-1 administration recombinant TGFβ shifted phenotype towards PD-1–. This led us hypothesis that interferes with program infiltrating As first measure compared expression between tumor, pigmented neoplasms, adjacent skin. isolated tumor-adjacent skin neoplasms were enriched for CD103. To uncover molecular pathways regulating tumor-residency performed bulk RNASeq on expressing skin, mice rejected their tumor. One pathway arose analysis was purinergic signaling (P2RX7, CD38, P2RY6). Competitive experiments P2RX7–/– indicated P2RX7-signaling negative regulates persistence tumors. Together, data suggest influences generation TRMcells mode escape provides new avenues population deeply.