Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival

Frontiers in Oncology

Oncology

Zahra Heidari¹  Shirin Tavana²  Zahra Mokhtari²  Marzieh Rezaei²  Mohammad Hossein Sanei³  Amirreza Dehghanian⁴  Zahra Faghih⁵ 

[1] Department of Biostatistics & Epidemiologyt, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran;Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran;Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran;Department of Pathology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran;Institute for Cancer Research (ICR), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;

关键词: colorectal cancer;    immune checkpoints;    programmed cell death protein-1;    T cell immunoglobulin and mucin-domain containing-3;    immunotherapy;    prognosis;   

DOI  :  10.3389/fonc.2023.1069696

 received in 2022-10-14, accepted in 2023-03-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundColorectal cancer (CRC) is a heterogeneous disease that complicates predicting patients’ prognosis and their response to treatment. CRC prognosis is influenced by the tumor microenvironment (TME). The immune system is a critical component of the TME. Programmed cell death receptor 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim3) are inhibitory immune checkpoints that regulate immune response and may provide prognostic power. However, the effect of their expressions and co-expressions on the CRC prognosis remains unclear. Accordingly, this study aimed to investigate the prognostic value of the CD8, CD3, PD-1, Tim3 expression, and PD-1/Tim3 co-expression in patients with CRC.Materials and MethodsOne hundred and thirty six patients with CRC who underwent curative surgery were enrolled in the study. Immunohistochemical staining was performed for PD-1, Tim3, CD8, and CD3, and the expression of each marker was evaluated in the center of the tumor (CT), invasive margin (IM), and adjacent normal-like tissue.ResultOur results indicated that high expression of PD-1 in IM was significantly associated with lower TNM stage, T-stage, M-stage, lack of metastasis, the presence of tertiary lymphoid structure (TLS), lack of recurrence (in the left-sided tumors), and larger tumor size (in right-sided tumors) (P<0.05). High expression of PD-1 in IM was also associated with improved overall survival (OS) in a subgroup of patients with high CD8 expression. High Tim3 expression in CT was associated with higher M-stage (M1) (in left-sided CRCs) (P<0.05). It was also associated with decreased OS in total cohort and left-sided CRCs and represented an independent prognostic factor for CRC patients in multivariate analysis. PD-1 and Tim3 co-expression had no synergistic effects on predicting OS.ConclusionOur findings suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD8, PD-1, and Tim3 depends on the primary tumor sides. We also showed that Tim3 could act as a prognostic factor and therapeutic target in CRC. This marker is probably a more preferred target for immunotherapy than PD-1, especially in left-sided CRCs.

【 授权许可】

Unknown   
Copyright © 2023 Mokhtari, Rezaei, Sanei, Dehghanian, Faghih, Heidari and Tavana