RT Journal Article
SR Electronic
T1 Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 1452
OP 1462
DO 10.1158/2326-6066.CIR-19-0934
VO 8
IS 11
A1 Tosti, Nadia
A1 Cremonesi, Eleonora
A1 Governa, Valeria
A1 Basso, Camilla
A1 Kancherla, Venkatesh
A1 Coto-Llerena, Mairene
A1 Amicarella, Francesca
A1 Weixler, Benjamin
A1 Däster, Silvio
A1 Sconocchia, Giuseppe
A1 Majno, Pietro Edoardo
A1 Christoforidis, Dimitri
A1 Tornillo, Luigi
A1 Terracciano, Luigi
A1 Ng, Charlotte K.Y.
A1 Piscuoglio, Salvatore
A1 von Flüe, Markus
A1 Spagnoli, Giulio
A1 Eppenberger-Castori, Serenella
A1 Iezzi, Giandomenica
A1 Droeser, Raoul Andre
YR 2020
UL http://cancerimmunolres.aacrjournals.org/content/8/11/1452.abstract
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.