058 Tissue-resident memory T cells in tumor immunity

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 can detect robust endogenous tumor-antigen specific response against measured IFN-γ ELISPOT pentamer staining. addition, after adoptive transfer into bearing hosts, OT-I expanded TdLN infiltrated tumor. To investigate properties first looked for expression CD103 CD69. found significantly more CD8 TILs co-expressing CD69 autochthonous BPO compared subcutaneous BPO-derived cell (22.3±2.4 vs 2.5±0.27 SEM). A subset also expressed markers tumors. contrast, isolated tumor-adjacent skin were enriched CD103.This led us hypothesis that interferes with program infiltrating cells. performed bulk RNASeq on expressing tumor, adjacent skin, mice rejected their respectively. From analysis identified several pathways appear regulate Of particular interest is CD101, which CD103+ TILs, receptors involved purinergic signaling pathway (P2RX7, CD38, P2RY6). Together, data suggest influences generation provide avenues population deeply.