期刊
SCIENCE
卷 374, 期 6575, 页码 1632-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaz7015
关键词
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资金
- National Institute of Health [1R01 CA219896-01A1, 1F32CA260769-01, R0AI143886, R01HL124112, R01AI109294, R01AI133822]
- US-Israel Binational Science Foundation [201332]
- Melanoma Research Alliance grant [4022024, 564449]
- American Association for Cancer Research Stand Up to Cancer grant [SU2C-AACRIRG-19-17]
- Andrew Sabin Family Fellows Program
- MD Anderson Cancer Center's Melanoma Moon Shots Program
- Department of Defense [W81XWH 16 1 0121]
- MD Anderson Cancer Center Multidisciplinary Research Program grant
- Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center
- American Society of Clinical Oncology and Conquer Cancer Foundation Career Development award [AWD0000627]
- Mark Foundation [AWD00004538]
- Longenbaugh-Torian Fund
- MD Anderson Cancer Center SPORE in Melanoma [P50CA221703]
- MD Anderson Physician Scientist Program
- Cancer Research Institute Irvington Fellowship Program
- Cancer Prevention and Research Institute of Texas Research Training Program [RP170067, RP210028, RP160097]
- US Department of State, Bureau of Educational and Cultural Affairs
- Fulbright Franco-Americaine Commission
- National Health and Medical Research Council of Australia CJ Martin Early Career Fellowship [1148680]
- National Institutes of Health T32 [CA 009599]
- MD Anderson NCI Cancer Center Support grant [P30 CA016672]
- Charles A. King Trust Postdoctoral Research Fellowship
- John M. Skibber Endowed Professorship
- Michael and Patricia Melanoma Research Endowment
- Columbia University Health Sciences NCI Cancer Center Support grant [P30 CA013696]
- Cancer Prevention and Research Institute of Texas grant [RR160089]
- Richard E. Haynes Distinguished Professor in Clinical Cancer Prevention
- American Cancer Society [RSG-17-049-01-NEC]
- National Institute of Health Intramural Research Program
- FLEX Synergy Award from the National Cancer Institute Center for Cancer Research
- National Cancer Institute Intramural Research Program
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- American Cancer Society/Melanoma Research Alliance grant [134148-MRAT-19-168-01]
- AIM at Melanoma Foundation
- National Institute of Health/National Cancer Institute grant [1 P50 CA221703-02, 1U54CA224070-03]
- Anne and John Mendelsohn Chair for Cancer Research
The study suggests that dietary fiber intake is associated with significantly improved progression-free survival in melanoma patients receiving ICB treatment, especially without the use of probiotics. Preclinical studies demonstrate that a low-fiber diet or probiotics can impair the treatment response to anti-PD-1 therapy, leading to a lower frequency of interferon-gamma-positive cytotoxic T cells in the tumor microenvironment.
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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