Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer

作者：Xing He, Yaorong Peng, Gui He, Huilin Ye, Liqiang Liu, Qixian Zhou, Juanyi Shi, Sha Fu, Jie Wang, Zhenyu Zhou, Wenbin Li · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04589-3 · 被引用次数：22 · 研究领域：Cancer Mechanisms and Therapy、Galectins and Cancer Biology、Cancer Immunotherapy and Biomarkers

BACKGROUND: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. METHODS: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. RESULTS: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced ...