ReviewLactate as a Regulator of Cancer Inflammation and ImmunitySantos, Nuno; Pereira-Nunes, Andreia; Baltazar, Fátima; Granja, Sara∗ Author Information 1Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga 4710-057 Portugal 2ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, 4710-057 Portugal ∗Correspondence: Sara Granja, E-mail: [email protected]. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND)http://creativecommons.org/licenses/by-nc-nd/4.0 Immunometabolism 1(2):e190015, October 2019. | DOI: 10.20900/immunometab20190015 Open Infographic Metrics Abstract Resistance to anti-cancer therapies is a consequence of adaptation of cancer cells but also of maladaptation of tumor-infiltrating immune cells. The opposing roles acquired by the immune system have to be faced in order to fight tumor growth and therapy resistance. Effector immune cells are recruited and activated but they are blocked by the strong immunosuppressive nature of the tumor microenvironment (TME). Immune evasion and deregulation of energy metabolism are two hallmarks of cancer that may be functionally linked. Malignant cells which present a high glycolytic phenotype, besides creating metabolic demanding environments that encroach on the function of tumor-infiltrating immune cells, also release immunosuppressive metabolites and by-products, such as lactate, forming a metabolic symbiosis with immune cells. This acidic TME has a strong impact in the profile of tumor-infiltrating immune cells, being instrumental for immunosuppression. Therefore, in this review, we focus on key molecular mechanisms by which lactate metabolically modulates immune cell response during tumor development and progression. Export Copyright © 2019 by the author(s). Licensee Hapres, London, United Kingdom.
