Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in...

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Immune cell infiltration is a key prognostic factor in colorectal cancer (CRC).
• The role of Interleukin-22 (IL22) in CRC pathogenesis and prognosis is not well understood, despite its known function in inflammatory bowel disease.

Purpose of the Study:

• To investigate the prognostic significance of IL22-producing immune cell infiltration in CRC.
• To explore the impact of IL22 on the tumor microenvironment composition and function in CRC.

Main Methods:

• Tissue microarrays (TMA) from CRC patients (n=425 testing, n=89 validation) were stained for IL22.
• Phenotypic characterization of IL22-producing cells was performed using flow cytometry.
• In vitro experiments assessed CRC cell chemokine production upon IL22 exposure and subsequent neutrophil migration.

Main Results:

• High IL22-positive immune cell infiltration was significantly associated with improved overall survival (OS) in CRC.
• IL22 was primarily produced by polyfunctional CD4+ and CD8+ T cells, co-producing IL17 and IFNγ.
• IL22 induced CRC cells to release neutrophil-recruiting chemokines (CXCL1, CXCL2, CXCL3), enhancing neutrophil migration.

Conclusions:

• IL22-producing T cell infiltration is a favorable prognostic marker in colorectal cancer.
• The beneficial effect of IL22 in CRC is mediated through the recruitment of neutrophils, which potentiate T cell responses.
• The interplay between IL22-producing T cells, neutrophils, and overall T cell infiltration defines a pro-survival tumor microenvironment in CRC.