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Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.
Bender, Mackenzie J; McPherson, Alex C; Phelps, Catherine M; Pandey, Surya P; Laughlin, Colin R; Shapira, Jake H; Medina Sanchez, Luzmariel; Rana, Mohit; Richie, Tanner G; Mims, Tahliyah S; Gocher-Demske, Angela M; Cervantes-Barragan, Luisa; Mullett, Steven J; Gelhaus, Stacy L; Bruno, Tullia C; Cannon, Nikki; McCulloch, John A; Vignali, Dario A A; Hinterleitner, Reinhard; Joglekar, Alok V; Pierre, Joseph F; Lee, Sonny T M; Davar, Diwakar; Zarour, Hassane M; Meisel, Marlies.
Afiliación
  • Bender MJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • McPherson AC; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
  • Phelps CM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Pandey SP; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Laughlin CR; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Shapira JH; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Medina Sanchez L; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Rana M; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Richie TG; Division of Biology, Kansas State University, Manhattan, KS, USA.
  • Mims TS; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.
  • Gocher-Demske AM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • Cervantes-Barragan L; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
  • Mullett SJ; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
  • Gelhaus SL; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
  • Bruno TC; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • Cannon N; Genetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • McCulloch JA; Genetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • Hinterleitner R; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • Joglekar AV; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Pierre JF; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.
  • Lee STM; Division of Biology, Kansas State University, Manhattan, KS, USA.
  • Davar D; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Zarour HM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Meisel M; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: marlies@pitt.edu.
Cell ; 186(9): 1846-1862.e26, 2023 04 27.
Article en En | MEDLINE | ID: mdl-37028428
ABSTRACT
The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 T cells abrogated Lr's antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr- and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally, we provide evidence for a potential role of I3A in promoting ICI efficacy and survival in advanced melanoma patients.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Limosilactobacillus reuteri / Microambiente Tumoral / Melanoma Límite: Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Limosilactobacillus reuteri / Microambiente Tumoral / Melanoma Límite: Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos