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Local anesthetics and immunotherapy: a novel combination to fight cancer

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Abstract

Intratumoral injection of oncolytic agents such as modified herpes simplex virus T-VEC or local administration of non-viral oncolytic therapies (such as radiofrequency, chemoembolization, cryoablation, or radiotherapy) can activate an anticancer immune response and hence trigger abscopal effects reducing secondary lesions. Preliminary data suggested that oncolytic treatments modulate tumor-infiltrating immune effectors and can be advantageously combined with the immune checkpoint inhibitors. Recent findings indicate that local anesthetics, which are usually used in the clinics to control surgical pain, also possess antineoplastic effects mimicking oncolytic treatments if they are injected into malignant lesions. Moreover, the association of local anesthetics with systemic immune checkpoint inhibition significantly improved overall survival in several preclinical tumor models. This may be explained by direct cytotoxic activity of local anesthetics and additional immune-related abscopal effects. We also summarize the molecular and cellular mechanisms by which the combination of local anesthetics and immunotherapy improves tumor control by the immune system.

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Funding

OK is supported by the Institut National du Cancer (INCa) and the DIM Elicit of the Ile-de-France. LB received a research grant by Bristol Myers Squibb Foundation France. GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Program on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; INCa; Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); the Leducq Foundation; a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM).

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Authors and Affiliations

  1. UMR1138, Centre de Recherche Des Cordeliers, Equipe Labellisée Par La Ligue Contre Le Cancer, Université de Paris, Sorbonne Université, INSERM, Institut Universitaire de France, Paris, France

    Lucillia Bezu, Oliver Kepp & Guido Kroemer

  2. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France

    Lucillia Bezu, Oliver Kepp & Guido Kroemer

  3. Service d’Anesthésie Gustave Roussy Cancer Campus, Villejuif, France

    Lucillia Bezu

  4. EuroPeriscope: Onco-Anaesthesiology Research Group, Brussels, Belgium

    Lucillia Bezu

  5. Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France

    Guido Kroemer

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  1. Lucillia Bezu
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  2. Oliver Kepp
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  3. Guido Kroemer
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Correspondence to Lucillia Bezu or Guido Kroemer.

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OK is a scientific co-founder of Samsara Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Samsara, Sanofi, Sotio, Vascage, and Vasculox/Tioma. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis, and metabolic disorders.

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This article is a contribution to the special issue on: Novel immunotherapeutic combinations moving forward: The modulation of the immunosuppressive microenvironment – Guest Editor: Mads Hald Andersen

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Bezu, L., Kepp, O. & Kroemer, G. Local anesthetics and immunotherapy: a novel combination to fight cancer. Semin Immunopathol 45, 265–272 (2023). https://doi.org/10.1007/s00281-022-00960-6

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