T Cells Expanded from PD-1+ Peripheral Blood Lymphocytes Share More Clones with Paired Tumor-Infiltrating Lymphocytes

Abstract Both tumor-infiltrating lymphocytes (TIL) and PD-1+ peripheral blood (PBL) are enriched for tumor-reactive clones recognizing known unknown tumor antigens. However, the relationship between T-cell receptor-? (TCR?) repertoires of TILs T cells expanded from paired PBLs, whether PBLs can be used to treat patients with cancer as TIL substitutes remain unclear. Here, we established a highly efficient protocol prepare polyclonal PBLs. A functional assay tetramer staining revealed that were relatively cells. Furthermore, deep TCR? sequencing data an average 11.29% (1.32%–29.06%; P = 0.015; n 8) tumor-resident clonotypes found in mean accumulated frequency was 35.11% (7.23%–78.02%; 0.017; 8). Moreover, treatment four patients, who failed multiline therapy developed acquired resistance anti-PD-1, autologous combined anti-PD-1 antibody elicited objective responses three them. These results indicate share more could substitutes. Significance: This study harnesses reactivity developing method expand these potential therapeutic strategy substitute cancer. See related commentary by Ladle, p. 1940