CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer
Open accessAbstract
T follicular helper cells (T FH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with T FH cell infiltration and improved survival in human cancer. Although human T FH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5 – ) T FH cells, here named T FH X13 cells, in promoting local memory B cell differentiation. T FH X13 cells potentially trigger tertiary lymphoid structure formation and thereby generate germinal center B cell responses at the tumor site. Follicular DCs are not potent CXCL13 producers in breast tumor tissues. We used the T FH cell markers PD-1 and ICOS to identify distinct effector and regulatory CD4 + T cell subpopulations in breast tumors. T FH X13 cells are an important component of the PD-1 hi ICOS int effector subpopulation and coexpanded with PD-1 int ICOS hi FOXP3 hi Tregs. IL2 deprivation induces CXCL13 expression in vitro with a synergistic effect from TGFβ1, providing insight into T FH X13 cell differentiation in response to Treg accumulation, similar to conventional T FH cell responses. Our data suggest that human T FH X13 cell differentiation may be a key factor in converting Treg-mediated immune suppression to de novo activation of adaptive antitumor humoral responses in the chronic inflammatory breast cancer microenvironment.
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A proportion of PD-1++ TILs with a Trm phenotype also express CXCL13, the ligand of CXCR5.
“A proportion of PD-1++ TILs with a Trm phenotype also express CXCL13, the ligand of CXCR5 [273-275].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [274]
The Introduction (page not provided) identifies PD-1-high CD4+ breast-cancer TIL that express CXCL13 and calls CXCR5 the CXCL13 receptor. The paper characterizes these cells as TFH-like, but the passages do not establish that the CXCL13-expressing PD-1-high cells have a tissue-resident memory (Trm) phenotype. (LLM, conf=0.87)
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- Authors
- Gu-Trantien, C., Migliori, E., Buisseret, L., de Wind, A., Brohée, S., Garaud, S., Noël, G., Dang Chi, V. L., Lodewyckx, J.-N., Naveaux, C., Duvillier, H., Goriely, S., Larsimont, D., & Willard-Gallo, K.
- Affiliations
- Molecular Immunology Unit,
- Anatomical Pathology,
- Breast Cancer Translational Research Laboratory,
- Hematology, and
- Université Libre de Bruxelles (BE)
- Corresponding author
- Willard-Gallo, Karen
- ORCID
- Venue
- JCI Insight
- Published
- 2017-06-02
- Volume
- 2
- Issue
- 11
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5453706
- OpenAlex
- W2620775812
- Cited by
- 368
- References
- 68
- Citations by year
- 2026: 27 · 2025: 36 · 2024: 35 · 2023: 48 · 2022: 63 · 2021: 68 · 2020: 39 · 2019: 24 · 2018: 24 · 2017: 3 · 2013: 1
- FWCI
- 11.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- European Regional Development Fund
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T follicular helper cells, CXCL13, breast cancer, tumor-infiltrating lymphocytes, regulatory T cells, tertiary lymphoid structures, germinal center B cells, PD-1, ICOS, follicular dendritic cells, TGF-β1, tumor microenvironment, immunosuppression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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