| First Author | Kogan D | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 5 | Pages | 1867-1872 |
| PubMed ID | 29438108 | Mgi Jnum | J:262861 |
| Mgi Id | MGI:6158753 | Doi | 10.1172/JCI96708 |
| Citation | Kogan D, et al. (2018) STAT3-enhancing germline mutations contribute to tumor-extrinsic immune evasion. J Clin Invest 128(5):1867-1872 |
| abstractText | Immune evasion and the suppression of antitumor responses during cancer progression are considered hallmarks of cancer and are typically attributed to tumor-derived factors. Although the molecular basis for the crosstalk between tumor and immune cells is an area of active investigation, whether host-specific germline variants can dictate immunosuppressive mechanisms has remained a challenge to address. A commonly occurring germline mutation (c.1162G>A/rs351855 G/A) in the FGFR4 (CD334) gene enhances signal transducer and activator of transcription 3 (STAT3) signaling and is associated with poor prognosis and accelerated progression of multiple cancer types. Here, using rs351855 SNP-knockin transgenic mice and Fgfr4-knockout mice, we reveal the genotype-specific gain of immunological function of suppressing the CD8/CD4+FOXP3+CD25+ regulatory T cell ratio in vivo. Furthermore, using knockin transgenic mouse models for lung and breast cancers, we establish the host-specific, tumor-extrinsic functions of STAT3-enhancing germline variants in impeding the tumor infiltration of CD8 T cells. Thus, STAT3-enhancing germline receptor variants contribute to immune evasion through their pleiotropic functions in immune cells. |
