Characteristics and anatomic location of PD-1+TCF1+ stem-like CD8 T cells in chronic viral infection and cancer

CD8 T cells play an essential role in anti-tumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in accordance with the progenitor-progeny relationship of TCF1+ stem-like and Tim-3+TCF1- more differentiated T cells. Here we investigated the characteristics of stem-like and differentiated CD8 T cells isolated from several murine tumor models and human lung cancer samples in terms of phenotypic and transcriptional features as well as their location compared to virus-specific CD8 T cells in the chronically LCMV-infected mice. We found that CD8 tumor-infiltrating lymphocytes (TILs) in both murine and human tumors exhibited overall similar phenotypic and transcriptional characteristics compared to corresponding subsets in the spleen of chronically infected mice. Primary and metastatic tumors in lung tissues were obtained from 19 patients with stage I-IV. Stem-like (Tim-3-CD28+ PD-1+) and exhausted (Tim-3+ PD-1+) human CD8 T cells were sorted from frozen TIL samples isolated from NSCLC patients. And naive (CCR7+CD45RA+CD58-CD95-) CD8 T cells from a healthy subject.