RT Journal Article
SR Electronic
T1 Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002836
DO 10.1136/jitc-2021-002836
VO 9
IS 10
A1 Peipei Wang
A1 Yueyun Chen
A1 Qingqin Long
A1 Qing Li
A1 Jiangfang Tian
A1 Ting Liu
A1 Yong Wu
A1 Zhenyu Ding
YR 2021
UL http://jitc.bmj.com/content/9/10/e002836.abstract
AB Background Immune checkpoint (IC) blockades (ICBs) significantly improve patients’ clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy.Methods RNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center.Results The results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence.Conclusion High expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.