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Cited by 303

The DOI matches its Crossref record; 111 of the 111 references it cites were found in a registry or an index.

T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants

Open access
Hirschhorn, Daniel, Budhu, Sadna, Kraehenbuehl, Lukas, Gigoux, Mathieu, Schröder, David, Chow, Andrew, Ricca, Jacob M., Gasmi, Billel, De Henau, Olivier, Mangarin, Levi Mark B., Li, Yanyun, Hamadene, Linda, Flamar, Anne-Laure, Choi, Hyejin, Cortez, Czrina A., Liu, Cailian, Holland, Aliya, Schad, Sara, Schulze, Isabell, Betof Warner, Allison, Hollmann, Travis J., Arora, Arshi, Panageas, Katherine S., Rizzuto, Gabrielle A., Duhen, Rebekka, Weinberg, Andrew D., Spencer, Christine N., Ng, David, He, Xue-Yan, Albrengues, Jean, Redmond, David, Egeblad, Mikala, Wolchok, Jedd D., Merghoub, Taha·2023·Cell
DOI 10.1016/j.cell.2023.03.007
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Abstract

Summary Cancer immunotherapies, including adoptive T cell transfer, can be ineffective because tumors evolve to display antigen loss variant clones. Therapies that activate multiple branches of the immune system may eliminate escape variants. Here we show that melanoma-specific CD4+ T cell therapy in combination with OX40 co-stimulation or CTLA-4 blockade can eradicate melanomas containing antigen escape variants. As expected, early on-target recognition of melanoma antigens by tumor-specific CD4+ T cells was required. Surprisingly, complete tumor eradication was dependent on neutrophils and partly dependent on inducible nitric oxide synthase. In support of these findings, extensive neutrophil activation was observed in mouse tumors and in biopsies of melanoma patients treated with immune checkpoint blockade. Transcriptomic and flow cytometry analyses revealed a distinct anti-tumorigenic neutrophil subset present in treated mice. Our findings uncover an interplay between T cells mediating the initial anti-tumor immune response, and neutrophils mediating the destruction of tumor antigen loss variants.

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Metadata

Authors
Hirschhorn, D., Budhu, S., Kraehenbuehl, L., Gigoux, M., Schröder, D., Chow, A., Ricca, J. M., Gasmi, B., De Henau, O., Mangarin, L. M. B., Li, Y., Hamadene, L., Flamar, A.-L., Choi, H., Cortez, C. A., Liu, C., Holland, A., Schad, S., Schulze, I., Betof Warner, A., Hollmann, T. J., Arora, A., Panageas, K. S., Rizzuto, G. A., Duhen, R., Weinberg, A. D., Spencer, C. N., Ng, D., He, X.-Y., Albrengues, J., Redmond, D., Egeblad, M., Wolchok, J. D., & Merghoub, T.
Venue
Cell
Publisher
Elsevier BV
Published
2023-03
Volume
186
Issue
7
Pages
1432-1447.e17
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2023.03.007
OpenAlex
W4361269839
Cited by
303
References
111
FWCI
31.27
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants. https://app.cochat.ai/papers/10.1016/j.cell.2023.03.007
The paper
Hirschhorn, D., Budhu, S., Kraehenbuehl, L., Gigoux, M., Schröder, D., Chow, A., Ricca, J. M., Gasmi, B., De Henau, O., Mangarin, L. M. B., Li, Y., Hamadene, L., Flamar, A.-L., Choi, H., Cortez, C. A., Liu, C., Holland, A., Schad, S., Schulze, I., . . . Merghoub, T. (2023). T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants. Cell. https://doi.org/10.1016/j.cell.2023.03.007

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.