Microbiota modulate tumoral immune surveillance in lung through a γδT17 immune cell-dependent mechanism

Abstract

Commensal bacteria are crucial to maintain immune homeostasis in mucosal tissues and disturbances in their ecology can impact disease susceptibility. Here we report evidence that commensal bacteria shape the efficiency of immune surveillance in mucosal tissues. Antibiotic-treated (Abt) mice were more susceptible to development of engrafted B16/F10 melanoma and Lewis lung carcinoma, exhibiting a shortened mean survival time with more numerous and larger tumor foci in the lungs. The defective anti-tumor response of Abt mice was independent of dehydration caused by antibiotics: host defenses relied upon intact commensal bacteria with no class specificity. Mechanistic investigations revealed a defective induction of the γδT17 cell response in lungs of Abt mice, here more aggressive tumor development was observed, possibly related to a reduction in IL-6 and IL-23 expression there. Adding normal γδT cells or supplementing IL-17 restored the impaired immune surveillance phenotype in Abt mice. Overall, our results demonstrated the importance of commensal bacteria in supporting the host immune response against cancer, defined an important role for γδT17 responses in the mechanism and suggested deleterious effects of antibiotic treatment on cancer susceptibility and progression.