Composition of the intestinal microbiome has been shown to impact generation of a tumor-specific immune response following chemotherapy and immune checkpoint blockade. We hypothesized that the local and intestinal microbiota may also impact immune activation and radiation response. We prospectively assessed the microbiota and T-cell repertoire of 30 cervical cancer patients throughout CRT. Greater diversity of the intestinal microbiome was associated with exceptional response and development of clonal T-cell expansion. Predominance of immunosuppressive Lactobacillus species in the cervix was associated with failure to expand clonal T-cells and decreased relapse-free survival. Patients with a robust response to CRT developed clonal expansion of T-cells, suggesting that highly radiation responsive cervical cancers generate an antigen specific immune response. Depletion of gut microbiome diversity and presence of vaginal Lactobacillus were associated with decreased presence of activated CD8 T-cell infiltration and decreased radiation response in an orthotopic model of HPV cancer, suggesting that microbial diversity is required for generation of effective antitumor immunity in radiation responsive HPV cancers.
Colbert, Lauren E. and Mikkelson, Megan and Medrano, Andrea Y. Delgado and Solley, Travis and Gopalakrishnan, Vancheswaran and Helmink, Beth and Previs, Rebecca J. and Eifel, Patricia J. and Jhingran, Anuja and Ramondetta, Lois M. and Futreal, Andrew M. and Jazaeri, Amir A. and Frumovitz, Michael and Schmeler, Kathleen M. and Hillman, Robert T. and Mathew, Geena and Sastry, Jagannadha and Dorta-Estremera, Stephanie and Venkatesan, Aradhana and Hutchinson, Diane and Ajami, Nadim J. and Stecklein, Shane R. and Taniguchi, Cullen M. and Okhuysen, Pablo C. and Petrosino, Joseph F. and Wargo, Jennifer and Hahn, Stephen M. and Klopp, Ann H., The Gut and Cervical Microbiome Promote Immune Activation and Response to Chemoradiation in Cervical Cancer (2018). Available at SSRN: https://ssrn.com/abstract=3199993 or http://dx.doi.org/10.2139/ssrn.3199993
This version of the paper has not been formally peer reviewed.
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