CD15+ Bone Marrow-derived Cells Are Regulators of Immune Response in ARG1-producing Colorectal Cancer Cells

Abstract

Background/aim: Bone marrow-derived cells regulate the antitumor functions of tumor infiltrating lymphocytes (TILs) through arginase 1 (ARG1)-dependent metabolism. This study examines which ARG1-producing lineage is responsible for the inhibitory function of TILs.

Materials and methods: Multiplexed immunohistochemistry was performed for CD11b, CD163, CD68, and CD15, together with ARG1 expression and CD3⁺ TIL infiltration estimation in human colorectal cancer specimens.

Results: Stratified survival analyses demonstrated that a large number of CD3⁺ TILs is a favorable prognostic factor in subgroups with a high level of ARG1⁺ infiltration and in the subgroup with a low level of ARG1^- CD15⁺ infiltration. Calculation of the ARG1⁺/ARG1^- ratio demonstrated that CD3⁺ TIL infiltration was prognostic in the subgroup with a low ARG1⁺/ARG1^- ratio for CD15⁺ cells, contrary to other lineages.

Conclusion: Tumor infiltrating CD15⁺ cells, the majority of which show polymorphonuclear features, are responsible for the ARG1-dependent T-cell dysfunction in human colorectal cancer.

Keywords: CD15; Cancer immunology; arginase 1; colorectal cancer; multiplex fluorescent labeling.