CD8-positive T Cell Infiltration With Human Leukocyte Antigen Class 1 Expression Predicts Patients With Stage IV Colorectal Cancer Survival

Abstract

Background/aim: The immune microenvironment in cancer correlates with cancer progression and patient prognosis. Cancer immune microenvironment evaluation, based on CD3⁺ and CD8⁺ T cell infiltration at the center and invasive margin of the tumor, is defined as the immunoscore. An international multicenter analysis revealed that the immunoscore can accurately predict the prognosis of patients with colorectal cancer (CRC) (stage I, II, and III). However, no markers are currently available to predict the prognosis in patients with stage IV CRC. We thus aimed to analyze the immune microenvironment in patients with stage IV CRC in this study.

Patients and methods: We analyzed the immune microenvironment of patients with stage IV CRC using immunohistochemical (IHC) staining. We evaluated the expressions of CD8 and the cases were divided into CD8 high (CD8^Hi) and CD8 low (CD8^Low) groups according to median CD8 expression. HLA class 1 (HLA1) expression was also evaluated using IHC staining and the cases were divided into HLA1^Hi group and HLA1^Low group according to 50% of HLA1 expression rate. CD8×HLA1 score was defined by the combination of CD8 and HLA1 expressions.

Results: CD8^Hi and HLA1^Hi cases were associated with better prognosis compared with CD8^Low and HLA1^Low cases according to a log-rank test, respectively. We defined a novel biomarker by combining CD8⁺ T-cell infiltration and HLA1 expression, referred to as the CD8×HLA1 score. We found that CD8×HLA1^Hi cases predicted patient prognosis better than CD8×HLA1^Int and CD8×HLA1^Low according to a log-rank test.

Conclusion: The combination of CD8⁺ T cell infiltration and HLA1 expression is crucial for cancer immune microenvironment evaluation in CRCs.

Keywords: CD8; CD8×HLA1 score; Colorectal cancer; HLA class 1; Stage IV.