10.3389/fonc.2019.01066.s002 Xi Li Xi Li Rouzheng Wang Rouzheng Wang Peiwen Fan Peiwen Fan Xuan Yao Xuan Yao Ling Qin Ling Qin Yanchun Peng Yanchun Peng Miaomiao Ma Miaomiao Ma Neil Asley Neil Asley Xuimei Chang Xuimei Chang Yaning Feng Yaning Feng Yunhui Hu Yunhui Hu Yonghong Zhang Yonghong Zhang Chris Li Chris Li Gregory Fanning Gregory Fanning Stephanie Jones Stephanie Jones Clare Verrill Clare Verrill David Maldonado-Perez David Maldonado-Perez Paul Sopp Paul Sopp Craig Waugh Craig Waugh Stephen Taylor Stephen Taylor Simon Mcgowan Simon Mcgowan Vincenzo Cerundolo Vincenzo Cerundolo Christopher Conlon Christopher Conlon Andrew McMichael Andrew McMichael Shichun Lu Shichun Lu Xiyan Wang Xiyan Wang Ning Li Ning Li Tao Dong Tao Dong Table_1_A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer.XLSX Frontiers 2019 T cells inhibitory receptor tumor-infiltrating lymphocytes tumor microenvironment combinatorial checkpoint blockade 2019-10-25 10:53:13 Dataset https://frontiersin.figshare.com/articles/dataset/Table_1_A_Comprehensive_Analysis_of_Key_Immune_Checkpoint_Receptors_on_Tumor-Infiltrating_T_Cells_From_Multiple_Types_of_Cancer_XLSX/10048460 <p>Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may reinvigorate antitumor T-cell immunity in those cancer patients while limiting immune-related adverse effects.</p><p>Method: This study recruited, in total, 172 primary cancer patients (131 were blood-tumor-matched patients) who were treatment-naïve prior to the surgeries or biopsies covering the eight most prevalent types of cancer. With access to fresh surgical samples, this study simultaneously investigated the ex vivo expression level of eight known immune checkpoint receptors [PD-1, cytotoxic T-lymphocyte antigen-4 [CTLA-4], T-cell immunoglobulin and mucin-domain containing-3 [Tim-3], 2B4, killer cell lectin like receptor G1 [KLRG-1], TIGIT, B- and T-lymphocyte attenuator [BTLA], and CD160] on tumor-infiltrating T cells (TILs) and paired circulating T cells in blood from a 131-patient cohort.</p><p>Results: We found increased an expression of PD-1 and Tim-3 but a decreased expression of BTLA on TILs when compared with peripheral blood from multiple types of cancer. Moreover, our co-expression analysis of key immune checkpoint receptors delineates “shared” subsets as PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4– and PD-1+TIGIT+2B4+Tim-3–KLRG-1–CTLA-4– from bulk CD8 TILs. Furthermore, we found that a higher frequency of advanced differentiation stage T cells (CD27–CCR7–CD45RA–) among the “shared” subset (PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4–) in bulk CD8 TILs was associated with poorly differentiated cancer type in cervical cancer patients.</p><p>Conclusions: To our knowledge, our study is the first comprehensive analysis of key immune checkpoint receptors on T cells in treatment-naïve, primary cancer patients from the eight most prevalent types of cancer. These findings might provide useful information for future design of mono-blockade/combinatorial blockades and/or genetically modified T-cell immunotherapy.</p>