| First Author | Xiong W | Year | 2023 |
| Journal | J Transl Med | Volume | 21 |
| Issue | 1 | Pages | 416 |
| PubMed ID | 37365574 | Mgi Jnum | J:359039 |
| Mgi Id | MGI:7785406 | Doi | 10.1186/s12967-023-04079-6 |
| Citation | Xiong W, et al. (2023) Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration. J Transl Med 21(1):416 |
| abstractText | BACKGROUND: Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion. METHODS: AOM/DSS model in Il11(-/-) and Apc(min/+)/Il11(-/-) mice were used to detect tumor growth and CD8(+) T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8(+) T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital. RESULTS: IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8(+) T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8(+) T infiltration were remarkably increased in the tumor tissues of Apc(min/+)/Il11(-/-) mice or Il11(-/-) mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNgamma-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. CONCLUSIONS: This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer. |
