NK cells beat T cells at early breast cancer control

ABSTRACT

Cancer immunosurveillance generally relies on adaptive immune programs executed by CD8⁺ T cells. Our findings demonstrate that CD8⁺ T cells fail to control early oncogenesis in a mouse model of luminal B breast cancer and suggest that natural killer (NK) cells may instead play a predominant role in this setting.

KEYWORDS:

• Hormonotherapy
• immune checkpoint blockers
• nicotinamide
• PD-1
• type I interferon
• tumor microenvironment

Acknowledgments

GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). The LG lab is supported by a Breakthrough Level 2 grant from the US Department of Defense (DoD), Breast Cancer Research Program (BRCP) (#BC180476P1), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a startup grant from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by industrial collaborations with Lytix (Oslo, Norway) and Phosplatin (New York, US), and by donations from Phosplatin (New York, US), the Luke Heller TECPR2 Foundation (Boston, US) and Sotio a.s. (Prague, Czech Republic).

Disclosures

AB, NB and GP have no conflicts of interest to disclose. GK has been holding research contracts with Bayer Healthcare, Genentech, Glaxo Smyth Kline, Institut Mérieux, Lytix Pharma, PharmaMar, Sotio and Vasculox, he is on the Board of Directors of the Bristol Myers Squibb Foundation France, and he is a scientific co-founder of everImmune, Samsara therapeutics and Therafast Bio. LG received consulting fees from OmniSEQ, Astra Zeneca, Inzen and the Luke Heller TECPR2 Foundation, and he is member of the Scientific Advisory Committee of Boehringer Ingelheim, The Longevity Labs and OmniSEQ.