Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

Overacre-Delgoffe, Abigail E.; Bumgarner, Hannah J.; Cillo, Anthony R.; Burr, Ansen H.P.; Tometich, Justin T.; Bhattacharjee, Amrita; Bruno, Tullia C.; Vignali, Dario A.A.; Hand, Timothy W.

doi:10.1016/j.immuni.2021.11.003

Cited by 318Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyGut microbiota and health

Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

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Overacre-Delgoffe, Abigail E., Bumgarner, Hannah J., Cillo, Anthony R., Burr, Ansen H.P., Tometich, Justin T., Bhattacharjee, Amrita, Bruno, Tullia C., Vignali, Dario A.A. +1 more·2021·Immunity

DOI 10.1016/j.immuni.2021.11.003PMC PMC8865366

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Abstract

The composition of the intestinal microbiota is associated with both the development of tumors and the efficacy of anti-tumor immunity. Here, we examined the impact of microbiota-specific T cells in anti-colorectal cancer (CRC) immunity. Introduction of Helicobacter hepaticus (Hhep) in a mouse model of CRC did not alter the microbial landscape but increased tumor infiltration by cytotoxic lymphocytes and inhibited tumor growth. Anti-tumor immunity was independent of CD8+ T cells but dependent upon CD4+ T cells, B cells, and natural killer (NK) cells. Hhep colonization induced Hhep-specific T follicular helper (Tfh) cells, increased the number of colon Tfh cells, and supported the maturation of Hhep+ tumor-adjacent tertiary lymphoid structures. Tfh cells were necessary for Hhep-mediated tumor control and immune infiltration, and adoptive transfer of Hhep-specific CD4+ T cells to Tfh cell-deficient Bcl6 fl/fl Cd4 Cre mice restored anti-tumor immunity. Thus, introduction of immunogenic intestinal bacteria can promote Tfh-associated anti-tumor immunity in the colon, suggesting therapeutic approaches for the treatment of CRC.

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In mouse colon cancer models, immune responses against gut microorganisms contribute to cancer immunosurveillance.
“As demonstrated in mouse models of colon cancer, immune responses directed against gut microorganisms participate in cancer immunosurveillance117.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [117]

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Authors: Overacre-Delgoffe, A. E., Bumgarner, H. J., Cillo, A. R., Burr, A. H. P., Tometich, J. T., Bhattacharjee, A., Bruno, T. C., Vignali, D. A. A., & Hand, T. W.
Affiliations: University of Pittsburgh (US)
Corresponding author: Hand, Timothy W.
ORCID: Overacre-Delgoffe, Abigail E.
Cillo, Anthony R.
Tometich, Justin T.
Bhattacharjee, Amrita
Bruno, Tullia C.
Vignali, Dario A.A.
Hand, Timothy W.
Venue: Immunity
Publisher: Elsevier BV
Published: 2021-12
Volume: 54
Issue: 12
Pages: 2812-2824.e4
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2021.11.003
PMC: PMC8865366
OpenAlex: W3215544807
Cited by: 318
References: 104
Citations by year: 2026: 73 · 2025: 71 · 2024: 77 · 2023: 70 · 2022: 25 · 2021: 2
FWCI: 16.39
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Children's Hospital of Pittsburgh
Recruitment and Assesment Centre
Damon Runyon Cancer Research Foundation
National Institutes of Health (T32AI089443, T32 5T32CA082084-18, R21 CA249074, P01 AI108545, R01 CA203689)
Bristol-Myers Squibb
F-star Therapeutics
Université Pierre et Marie Curie
Department of Pediatrics, University of Florida
Eden Hall Foundation
University of Pittsburgh
Astellas Pharma US
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: colorectal cancer, gut microbiota, T follicular helper cells, tertiary lymphoid structures, antitumor immunity, Helicobacter hepaticus, CD4+ T cells, B cells, natural killer cells, BCL6, tumor-infiltrating lymphocytes, adoptive T cell therapy
MeSH terms: Gastrointestinal Microbiome, Tertiary Lymphoid Structures, T Follicular Helper Cells, Animals, Colon, Disease Models, Animal, Humans, Killer Cells, Natural, Colorectal Neoplasms, CD4-Positive T-Lymphocytes, B-Lymphocyte Subsets, Lymphocytes, Tumor-Infiltrating, Helicobacter Infections, Helicobacter hepaticus, Mice, Proto-Oncogene Proteins c-bcl-6

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Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

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