PT  - JOURNAL ARTICLE
AU  - Tosti, Nadia
AU  - Cremonesi, Eleonora
AU  - Governa, Valeria
AU  - Basso, Camilla
AU  - Kancherla, Venkatesh
AU  - Coto-Llerena, Mairene
AU  - Amicarella, Francesca
AU  - Weixler, Benjamin
AU  - Däster, Silvio
AU  - Sconocchia, Giuseppe
AU  - Majno, Pietro Edoardo
AU  - Christoforidis, Dimitri
AU  - Tornillo, Luigi
AU  - Terracciano, Luigi
AU  - Ng, Charlotte K.Y.
AU  - Piscuoglio, Salvatore
AU  - von Flüe, Markus
AU  - Spagnoli, Giulio
AU  - Eppenberger-Castori, Serenella
AU  - Iezzi, Giandomenica
AU  - Droeser, Raoul Andre
TI  - Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer
AID  - 10.1158/2326-6066.CIR-19-0934
DP  - 2020 Nov 01
TA  - Cancer Immunology Research
PG  - 1452--1462
VI  - 8
IP  - 11
4099  - http://cancerimmunolres.aacrjournals.org/content/8/11/1452.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/11/1452.full
SO  - Cancer Immunol Res2020 Nov 01; 8
AB  - Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role in inflammatory bowel disease, but its relevance in colorectal cancer remains unclear. Here, we addressed the prognostic significance of IL22+ cell infiltration in colorectal cancer and its effects on the composition of tumor microenvironment. Tissue microarrays (TMA) were stained with an IL22-specific mAb, and positive immune cells were counted by expert pathologists. Results were correlated with clinicopathologic data and overall survival (OS). Phenotypes of IL22-producing cells were assessed by flow cytometry on cell suspensions from digested specimens. Chemokine production was evaluated in vitro upon colorectal cancer cell exposure to IL22, and culture supernatants were used to assess neutrophil migration in vitro. Evaluation of a testing (n = 425) and a validation TMA (n = 89) revealed that high numbers of IL22 tumor-infiltrating immune cells were associated with improved OS in colorectal cancer. Ex vivo analysis indicated that IL22 was produced by CD4+ and CD8+ polyfunctional T cells, which also produced IL17 and IFNγ. Exposure of colorectal cancer cells to IL22 promoted the release of the neutrophil-recruiting chemokines CXCL1, CXCL2, and CXCL3 and enhanced neutrophil migration in vitro. Combined survival analysis revealed that the favorable prognostic significance of IL22 in colorectal cancer relied on the presence of neutrophils and was enhanced by T-cell infiltration. Altogether, colorectal cancer–infiltrating IL22-producing T cells promoted a favorable clinical outcome by recruiting beneficial neutrophils capable of enhancing T-cell responses.