Using a High-Fiber Diet to Improve Melanoma Patients’ Response to Immunotherapy


ASPIRE Award (2019-Present)

Jennifer McQuade, MD, MS (Principal); Jennifer Wargo, MD, MMSc; and Carrie Daniel-MacDougall, PhD, MPH, The University of Texas MD Anderson Cancer Center

Blockade of immune inhibitory receptors PD1 and CTLA-4 can reinvigorate anti-tumor T cells eliciting tumor regression and improved survival in melanoma and several other tumor types. However, just under half of all melanoma patients are resistant to these immune-based therapies. Researchers in the McQuade lab found melanoma patients on a fiber-rich diet are five times more likely to respond to anti-PD1 immunotherapy than patients on a low-fiber diet. Furthermore, patients on a fiber-rich diet had a greater abundance of gut bacteria known to be associated with ICB response and known to be involved in fiber metabolism. To determine if high-fiber diet intervention can increase systemic and anti-tumor immunity, the McQuade group has initiated a randomized, controlled trial in metastatic melanoma. Patients receiving anti-PD1 in either the adjuvant or unresectable setting will be randomized to a high-fiber diet or control diet, and both T-cell activation and promotion of CD8 T-cell memory will be assessed in the periphery and tumor microenvironment. Parallel studies in anti-PD1 treated, germ-free, melanoma tumor-bearing mice will be carried out using a fecal microbiota transplant (FMT) model. Mice will receive FMT from pre- and post-diet specimens obtained from melanoma patients in an ongoing fiber feeding study. Microbiome, immune profiling, and tumor growth rates will be compared across treatment groups to determine if post-dietary intervention FMT, through alteration of the microbiome, can enhance anti-PD1 efficacy. Confirmation of diet-enhanced anti-tumor immunity will support initiation of larger trials evaluating the impact of fiber-rich dietary intervention on immunotherapy outcomes.

PUBLISHED RESEARCH

Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, Peterson CB, Wong MC, Morad G, Rodgers T, Badger JH, Helmink BA, Andrews MC, Rodrigues RR, Morgun A, Kim YS, Roszik J, Hoffman KL, Zheng J, Zhou Y, Medik YB, Kahn LM, Johnson S, Hudgens CW, Wani K, Gaudreau PO, Harris AL, Jamal MA, Baruch EN, Perez-Guijarro E, Day CP, Merlino G, Pazdrak B, Lochmann BS, Szczepaniak-Sloane RA, Arora R, Anderson J, Zobniw CM, Posada E, Sirmans E, Simon J, Haydu LE, Burton EM, Wang L, Dang M, Clise-Dwyer K, Schneider S, Chapman T, Anang NAS, Duncan S, Toker J, Malke JC, Glitza IC, Amaria RN, Tawbi HA, Diab A, Wong MK, Patel SP, Woodman SE, Davies MA, Ross MI, Gershenwald JE, Lee JE, Hwu P, Jensen V, Samuels Y, Straussman R, Ajami NJ, Nelson KC, Nezi L, Petrosino JF, Futreal PA, Lazar AJ, Hu J, Jenq RR, Tetzlaff MT, Yan Y, Garrett WS, Huttenhower C, Sharma P, Watowich SS, Allison JP, Cohen L, Trinchieri G, Daniel CR, Wargo JA. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021.

Vellano CP, White MG, Andrews MC, Chelvanambi M, Witt RG, Daniele JR, Titus M, McQuade JL, Conforti F, Burton EM, Lastrapes MJ, Ologun G, Cogdill AP, Morad G, Prieto P, Lazar AJ, Chu Y, Han G, Khan MAW, Helmink B, Davies MA, Amaria RN, Kovacs JJ, Woodman SE, Patel S, Hwu P, Peoples M, Lee JE, Cooper ZA, Zhu H, Gao G, Banerjee H, Lau M, Gershenwald JE, Lucci A, Keung EZ, Ross MI, Pala L, Pagan E, Segura RL, Liu Q, Borthwick MS, Lau E, Yates MS, Westin SN, Wani K, Tetzlaff MT, Haydu LE, Mahendra M, Ma X, Logothetis C, Kulstad Z, Johnson S, Hudgens CW, Feng N, Federico L, Long GV, Futreal PA, Arur S, Tawbi HA, Moran AE, Wang L, Heffernan TP, Marszalek JR, Wargo JA. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy. Nature. 2022.

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