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CD28 costimulation promotes an antitumor CD8+ T cell response in myeloid antigen-presenting cell niches

Cellular & Molecular Immunology volume 19, pages 147–149 (2022)Cite this article

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Ectopic lymphoid structures found within the tumor stroma, such as tertiary lymphoid structures (TLSs), are predictive markers of immune checkpoint blockade (ICB) in solid tumors. In a recent study in Cancer Cell, Duraiswamy et al. highlighted other immune structures, such as myeloid antigen-presenting cell (APC) niches, in the context of high-grade serous ovarian cancers (HGSOCs) [1]. In these structures, programmed cell death receptor 1 (PD-1)+ tumor-infiltrating T lymphocytes (TILs) undergo a full activation program (a license to kill) via the CD28 costimulatory molecule during PD-1 blockade in HGSOC.

Immune checkpoint blockade (ICB) therapy has revolutionized the management of many cancers, but the results in ovarian cancer remain disappointing. Initial single-agent studies in multiple relapse situations have shown response rates of 10–15%. In addition, phase III studies with more than 1000 patients with stage III–IV epithelial ovarian cancer treated with surgery as first-line treatment have shown no real benefit from the addition of an anti-programmed death-ligand 1 (PD-L1) mAb in the initial management of this type of cancer [2]. However, ovarian cancer is theoretically an excellent candidate to respond to immunotherapy (PD-L1 expression, lymphocyte infiltrate).

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Fig. 1

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Acknowledgements

We thank Pierre-Louis Bernard for his help in generating the figure. The figure was created with BioRender.com.

Funding

The team “Immunity and Cancer” was labeled by the Fondation pour la Recherche Médicale “Equipe FRM DEQ20180339209”. DO is Senior Scholar of the Institut Universitaire de France.

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Authors and Affiliations

  1. Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068; CNRS, UMR7258; Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France

    Jacques A. Nunès & Daniel Olive

  2. IBiSA Immunomonitoring Platform, CRCM, Institut Paoli-Calmettes, Marseille, France

    Daniel Olive

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  1. Jacques A. Nunès
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Correspondence to Jacques A. Nunès.

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JAN has no competing interests. DO is a cofounder and shareholder of Imcheck Therapeutics, Alderaan Biotechnology and Emergence Therapeutics and receives research funds from Imcheck Therapeutics, Alderaan Biotechnology, Cellectis and Emergence Therapeutics. All of these are outside of the submitted work.

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Nunès, J.A., Olive, D. CD28 costimulation promotes an antitumor CD8+ T cell response in myeloid antigen-presenting cell niches. Cell Mol Immunol 19, 147–149 (2022). https://doi.org/10.1038/s41423-021-00818-1

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