Suppression of FIP200 and autophagy by tumor-derived lactate promotes naïve T cell apoptosis and affects tumor immunity

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Science Immunology  17 Nov 2017:
Vol. 2, Issue 17, eaan4631
DOI: 10.1126/sciimmunol.aan4631

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Tumor immunity flounders without FIP200

The tumor microenvironment impairs the function of effector and memory T cells, but its effect on naïve T cells is not well understood. Xia et al. show that the autophagy component FAK family–interacting protein of 200 kDa (FIP200) is critical for promoting antitumor responses mediated by T cells. Ovarian cancer patients and mouse tumor models had significantly higher rates of apoptosis and impaired autophagy in naïve T cells, as well as the selective loss of FIP200, which disrupted the balance of pro- and antiapoptotic factors. Tumor-derived lactate was shown to suppress FIP200 expression, thus causing enhanced apoptosis and attenuated antitumor responses.