The survey in the role of LAG3+ tumor-infiltrating lymphocytes in colorectal cancer prognosis; Relationship with sidedness

Abstract

Background: The interplay between tumor-infiltrating lymphocytes (TILs) and tumor cells is a major determining factor in cancer progression. CD45RO seems to be a reliable indicator for predicting prognosis and disease outcome, along with CD3 and CD8 markers. LAG-3 is another important marker that overexpresses on TILs in a variety of cancers and is associated with disease prognosis; however, its prognostic impact is controversial. Hence, in the present study, we aimed to investigate the presence of CD45RO+, LAG3+, CD3+, and CD8+ lymphocytes in CRC tumor tissues and their association with clinicopathological parameters of the disease as well as patients' survival, according to primary tumor locations.Methods: Expression of CD45RO, LAG3, CD3, and CD8 was Immunohistochemically analyzed in tissue sections from 136 patients with CRC. The percentage of TILs expressing these markers were separately determined in the invasive margin (IM) and center of the tumor (CT). Their associations with clinical factors and survival were analyzed in the entire cohort, and in the subgroups of patients with right and left/rectum tumors.Results: Based on our observation, CD45RO+ and CD3+ lymphocytes were the most frequent infiltrated cells in both CT and IM regions of colon tumor tissue. On the other hand, LAG3+ lymphocytes were the least frequent subset in both areas. In univariate analysis, high score of CD45RO in IM was associated with better overall survival in the entire cohort. High score of CD8 and CD45RO in IM were also associated with improved overall survival in right-sided tumors. However, CD45RO expression correlated with advanced TNM stages (III/IV), in the entire cohort and in right-sided tumors. In the case of LAG3, although the association between the expression of this marker and survival was not found, LAG3+ TILs in CT were associated with higher T-stages in the entire cohort.Conclusions: Our findings suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD45RO and LAG3 depends on the primary tumor sides. Our results collectively demonstrated that infiltration of CD45RO+ lymphocytes in IM could be an independent prognostic factor in a site-dependent manner.