1189 PD-1 blockade may promote not only the reactivation of preexisting tumor-specific T cell clones but also the infiltration of new clones

Immune checkpoint inhibitors (ICIs) can sometimes produce a durable response in melanoma patients. However, the clinical benefits are usually limited. We attempted to elucidate dynamics of tumor infiltrating lymphocytes (TILs) responder; we tracked TILs metastatic tissue during anti-PD-1 therapy obtain clues for maximizing effect ICIs. First, performed single cell RNA and T receptor (TCR) sequencing (scRNA/TCR-seq) using pre-and post- biopsy samples. included skewed clonotypes, which were characterized by exhaustion (Tex) or nonexhaustion signatures (Tnon-ex). Among those Tex, but not Tnon-ex, cluster responded autologous lines. In post-sample, only preexisting, also non-preexisting tumor-specific clonotypes Tex detected. To address origin such scRNA/TCR-seq was paired TILs, peripheral blood (PBLs), nonmetastatic draining lymph node (DLN) derived from 5 non-small lung cancer head neck As result, considerable number could be found DLNs, although they rarely detected PBLs. These findings suggest that PD-1 blockade promotes activation preexisting cells infiltration cells, most likely DLN. Our raise an important question about best time combine local (e.g., surgery, radiotherapy, oncolytic virus etc.)