Figure S9 from Vγ9Vδ2 T Cells Express an Antitumor Profile Associated with Anti–PD-(L)1 Responses and Activation Defects Restored by Anti-BTN3A in Triple-Negative Breast Cancer

Fattori, Stéphane; Gorvel, Laurent; Rouviére, Marie-Sarah; Granjeaud, Samuel; Ben Amara, Amira; Richaud, Manon; Boucherit, Nicolas; Tarpin, Carole; Pakradouni, Jihane; Hédou, Julien; Bellan, Grégoire; Gaudilliere, Brice; Charafe-Jauffret, Emmanuelle; Houvenaeghel, Gilles; Lambaudie, Eric; Bertucci, François; Fournié, Jean-Jacques; Gonçalves, Anthony; Rochigneux, Philippe; Chrétien, Anne-Sophie; Olive, Daniel

doi:10.1158/2326-6066.30255232

Figure S9 from Vγ9Vδ2 T Cells Express an Antitumor Profile Associated with Anti–PD-(L)1 Responses and Activation Defects Restored by Anti-BTN3A in Triple-Negative Breast Cancer

journal contribution

posted on 2025-10-01, 07:22 authored by Stéphane Fattori, Laurent Gorvel, Marie-Sarah Rouviére, Samuel Granjeaud, Amira Ben Amara, Manon Richaud, Nicolas Boucherit, Carole Tarpin, Jihane Pakradouni, Julien Hédou, Grégoire Bellan, Brice Gaudilliere, Emmanuelle Charafe-Jauffret, Gilles Houvenaeghel, Eric Lambaudie, François Bertucci, Jean-Jacques Fournié, Anthony Gonçalves, Philippe Rochigneux, Anne-Sophie Chrétien, Daniel Olive

<p>Vg9Vd2 T cells are associated with better clinical responses to PD–(L)1 blockade therapy (related to Figure 5).</p>

Funding

Institut National Du Cancer (INCa)

Site de Recherche Intégrée en Cancérologie (SIRIC) Marseille

Fondation de France (Foundation of France)

Cancéropôle Provence–Alpes–Côte d’Azur

Fondation pour la Recherche Médicale (FRM)

History

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DOI - Is supplement to Vγ9Vδ2 T Cells Express an Antitumor Profile Associated with Anti–PD-(L)1 Responses and Activation Defects Restored by Anti-BTN3A in Triple-Negative Breast Cancer

ARTICLE ABSTRACT

Vγ9Vδ2 (TCRVγ9+ TCRVδ2+) T cells are promising immunotherapeutic targets with effective antitumor properties in both in vitro and preclinical models of triple-negative breast cancer (TNBC). However, no information about their potential role in the context of human TNBC progression and response to immunotherapy has been reported. One key reason for this is the scarcity of Vγ9Vδ2 T-cell infiltrates relative to their Vδ1 (TCRVδ1+) and αβCD8 (TCRαβ+ CD8αβ+) T-cell counterparts. We provide comprehensive single-cell profiling of Vγ9Vδ2 T cells from patients with TNBC, prior to and following PD-(L)1 blockade therapy. We report that baseline Vγ9Vδ2 T-cell infiltrate expressing a unique cytotoxic type I phenotype could be associated with improved survival in patients with TNBC. Vγ9Vδ2 T cells harboring characteristics of enhanced antitumor activity (KLRC1+) were further associated with improved response to PD-(L)1 blockade therapy in patients with TNBC. Vγ9Vδ2 T cells had low expression levels of T-cell exhaustion (PD-1LowTOXLow) and T-cell receptor signaling hallmarks compared with Vδ1 and αβCD8 T cells, along with skewed differentiation profiles toward early effector memory phenotypes, both before and after anti–PD-1 therapy in TNBC tumors. Consistently, we observed limited activity of anti–PD-1 on tumor-infiltrating Vγ9Vδ2 T cells. In vitro, the use of anti–butyrophilin-3A antibodies in addition to anti–PD-1 reinvigorated the cytotoxic type I functions of peripheral Vγ9Vδ2 T cells from patients with breast cancer. Together, these data provide a rationale for Vγ9Vδ2 T cell–based combination therapy in patients with TNBC.