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

Anticancer Res. 2022 Jan;42(1):459-470. doi: 10.21873/anticanres.15504.


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.

MeSH terms

  • Aged
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Arginase / genetics*
  • Bone Marrow
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Immunity / genetics
  • Lewis X Antigen / genetics*
  • Lewis X Antigen / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Cell Surface / genetics


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CD68 antigen, human
  • Lewis X Antigen
  • Receptors, Cell Surface
  • ARG1 protein, human
  • Arginase