Local anesthetics and immunotherapy: a novel combination to fight cancer

Lucillia Bezu1,2,3,4, Oliver Kepp1,2, Guido Kroemer5,1,2
1Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France
2UMR1138, 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
3Service d’Anesthésie Gustave Roussy Cancer Campus, Villejuif, France
4EuroPeriscope: Onco-Anaesthesiology Research Group, Brussels, Belgium
5Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France

Tóm tắt

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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