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This study received support from National Institute of Health grant 1R01 CA219896-01A1 (J.A.W.); US-Israel Binational Science Foundation grant 201332 (J.A.W.); the Melanoma Research Alliance grant 4022024 (J.A.W.); American Association for Cancer Research Stand Up to Cancer grant SU2C-AACRIRG-19-17 (J.A.W.); the Andrew Sabin Family Fellows Program (J.A.W. and C.R.D.); MD Anderson Cancer Center's Melanoma Moon Shots Program (J.A.W., J.L.M., C.R.D., M.A.D., H.A.T., J.E.G., and E.M.B.); and the Melanoma Research Alliance grant 564449 (L.C., J.A.W., and J.L.M.). The authors additionally received support from Department of Defense grant W81XWH 16 1 0121 (J.A.W.); the MD Anderson Cancer Center Multidisciplinary Research Program grant (J.A.W.); the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center (J.A.W., H.A.T., P.S., and J.P.A.); American Society of Clinical Oncology and Conquer Cancer Foundation Career Development award AWD0000627 (J.L.M.); the Elkins Foundation (J.L.M.); the Seerave Foundation (J.L.M.); Rising Tide Foundation grant AWD00004505 (J.L.M.); the Mark Foundation grant AWD00004538 (J.L.M.); the Longenbaugh-Torian Fund (J.L.M.); the MD Anderson Cancer Center SPORE in Melanoma P50CA221703 (M.A.D., H.A.T., I.C.G., J.A.W., S.P.P., J.E.L., J.E.G., A.J.L., and J.L.M.); the MD Anderson Physician Scientist Program (J.L.M.); the Cancer Research Institute Irvington Fellowship Program (M.V.); Cancer Prevention and Research Institute of Texas Research Training Program RP170067 (A.P.C., J.T., and J.Z.); Cancer Prevention and Research Institute of Texas Research Training Program RP210028 (L.M.K.); the US Department of State, Bureau of Educational and Cultural Affairs (A.P.C.); the Fulbright Franco-Americaine Commission (A.P.C.); Cancer Prevention and Research Institute of Texas Research Training Program RP160097 (X.Z.); National Health and Medical Research Council of Australia CJ Martin Early Career Fellowship grant 1148680 (M.C.A.); National Institutes of Health T32 CA 009599 (M.G.W. and B.A.H.); the MD Anderson NCI Cancer Center Support grant P30 CA016672 (M.G.W., B.A.H., C.R.D., K.C.-D., and C.B.P.); National Institute of Health grant 1F32CA260769-01 (G.Mo.); the Charles A. King Trust Postdoctoral Research Fellowship (Y.Y. and C.H.); the John M. Skibber Endowed Professorship (J.E.G.); the Michael and Patricia Melanoma Research Endowment (J.E.G.); National Institute of Health grant R0AI143886 (J.H.); Columbia University Health Sciences NCI Cancer Center Support grant P30 CA013696 (J.H.); National Institute of Health grant R01HL124112 (R.R.J.); Cancer Prevention and Research Institute of Texas grant RR160089 (R.R.J.); National Institute of Health grant R01AI109294 (S.S.W.); National Institute of Health grant R01AI133822 (S.S.W.); the Richard E. Haynes Distinguished Professor in Clinical Cancer Prevention (L.C.); American Cancer Society grant RSG-17-049-01-NEC (C.R.D.); the National Institute of Health Intramural Research Program (E.P.-G., C.-P.D., and G.Me.); FLEX Synergy Award from the National Cancer Institute Center for Cancer Research (E.P.-G., C.-P.D., and G.Me.); the National Cancer Institute Intramural Research Program (J.A.M., M.V., J.H.B., R.R.R., and G.T.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.A.D.); American Cancer Society/Melanoma Research Alliance grant 134148-MRAT-19-168-01 (M.A.D.); the AIM at Melanoma Foundation (M.A.D.); the National Institute of Health/National Cancer Institute grant 1 P50 CA221703-02 (M.A.D.); the National Institute of Health/National Cancer Institute grant 1U54CA224070-03 (M.A.D.); Cancer Fighters of Houston (M.A.D.); and the Anne and John Mendelsohn Chair for Cancer Research (M.A.D.).

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Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response

Publicated to:SCIENCE. 374 (6575): 1632-+ - 2021-12-24 374(6575), DOI: 10.1126/science.aaz7015

Authors: Spencer, Christine N.; McQuade, Jennifer L.; Gopalakrishnan, Vancheswaran; McCulloch, John A.; Vetizou, Marie; Cogdill, Alexandria P.; Khan, Md A. Wadud; Zhang, Xiaotao; White, Michael G.; Peterson, Christine B.; Wong, Matthew C.; Morad, Golnaz; Rodgers, Theresa; Badger, Jonathan H.; Helmink, Beth A.; Andrews, Miles C.; Rodrigues, Richard R.; Morgun, Andrey; Kim, Young S.; Roszik, Jason; Hoffman, Kristi L.; Zheng, Jiali; Zhou, Yifan; Medik, Yusra B.; Kahn, Laura M.; Johnson, Sarah; Hudgens, Courtney W.; Wani, Khalida; Gaudreau, Pierre-Olivier; Harris, Angela L.; Jamal, Mohamed A.; Baruch, Erez N.; Perez-Guijarro, Eva; Day, Chi-Ping; Merlino, Glenn; Pazdrak, Barbara; Lochmann, Brooke S.; Szczepaniak-Sloane, Robert A.; Arora, Reetakshi; Anderson, Jaime; Zobniw, Chrystia M.; Posada, Eliza; Sirmans, Elizabeth; Simon, Julie; Haydu, Lauren E.; Burton, Elizabeth M.; Wang, Linghua; Dang, Minghao; Clise-Dwyer, Karen; Schneider, Sarah; Chapman, Thomas; Anang, Nana-Ama A. S.; Duncan, Sheila; Toker, Joseph; Malke, Jared C.; Glitza, Isabella C.; Amaria, Rodabe N.; Tawbi, Hussein A.; Diab, Adi; Wong, Michael K.; Patel, Sapna P.; Woodman, Scott E.; Davies, Michael A.; Ross, Merrick, I; Gershenwald, Jeffrey E.; Lee, Jeffrey E.; Hwu, Patrick; Jensen, Vanessa; Samuels, Yardena; Straussman, Ravid; Ajami, Nadim J.; Nelson, Kelly C.; Nezi, Luigi; Petrosino, Joseph F.; Futreal, P. Andrew; Lazar, Alexander J.; Hu, Jianhua; Jenq, Robert R.; Tetzlaff, Michael T.; Yan, Yan; Garrett, Wendy S.; Huttenhower, Curtis; Sharma, Padmanee; Watowich, Stephanie S.; Allison, James P.; Cohen, Lorenzo; Trinchieri, Giorgio; Daniel, Carrie R.; Wargo, Jennifer A.;

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Abstract

Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti-programmed cell death 1 (anti-PD-1)-based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-gamma-positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.

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