TNFR1 expression on cancer cell is critical for immunoescape, shaping an immunosuppressive tumor microenvironment [EO771]

Experiments performed in transplantable tumors in which we silenced TNFR1 with CRISPR/Cas9 showed the inability of the TNFR1 KO variants to engraft in immunocompetent hosts, whilst engraftment in immunodeficient or CD8 T lymphocyte-depleted mice was preserved.

The mechanism was related to secondary inflammatory mediators elicited by TNFα in malignant cells themselves, including CXCR1/2 chemokines and interestingly TNFα itself. As a result, TNFR1 KO variants recruited drastically fewer myeloid-derived suppressor cells into the tumor microenvironment, thus explaining the immune escape of the WT variants. Interestingly, TNFR1-sufficient tumor cells, when co-engrafted with the TNFR1 KO variants, rescued tumorigenicity of the same tumor lesion but not of a distantly implanted TNFR1 KO tumor.