THE EFFECT OF TUMOR ACIDITY ON ANTITUMOR IMUNE RESPONSE - A SYSTEMATIC REVIEW.

Abstract

Objective This study aims to compile and discuss the mechanisms underlying how the presence of lactic acid and/or tumor acidity results in an antitumor immune response inefficiency. Study Design A systematic review was conducted according to PRISMA guidelines and registered at PROSPERO. The search was performed on PubMed and EMBASE and designed to identify all studies evaluating the effects of tumor-generated acidosis and/or lactic acid on the immune response. Literature reviews, conference abstracts, and scientific articles not written in English were excluded. Results This study identified 9451 references; after reading abstracts/titles, 145 were selected for full-text reading, resulting in 102 selected texts. The main findings detected were: alteration in receptors, ligands, and adhesion molecules on immune cells; decreased cytotoxicity of effector cells; polarization of macrophages into M2 phenotypes; disturbed maturation of monocytes; imbalanced cytokine production and secretion; decreased cell proliferation and motility; unsettled activation and cell function; distorted activation of signaling pathways. Conclusion The tumor microenvironment can change important key pathways in tumor development, and the neutralization of the tumor acidity would benefit the development of new immunotherapies. This study aims to compile and discuss the mechanisms underlying how the presence of lactic acid and/or tumor acidity results in an antitumor immune response inefficiency. A systematic review was conducted according to PRISMA guidelines and registered at PROSPERO. The search was performed on PubMed and EMBASE and designed to identify all studies evaluating the effects of tumor-generated acidosis and/or lactic acid on the immune response. Literature reviews, conference abstracts, and scientific articles not written in English were excluded. This study identified 9451 references; after reading abstracts/titles, 145 were selected for full-text reading, resulting in 102 selected texts. The main findings detected were: alteration in receptors, ligands, and adhesion molecules on immune cells; decreased cytotoxicity of effector cells; polarization of macrophages into M2 phenotypes; disturbed maturation of monocytes; imbalanced cytokine production and secretion; decreased cell proliferation and motility; unsettled activation and cell function; distorted activation of signaling pathways. The tumor microenvironment can change important key pathways in tumor development, and the neutralization of the tumor acidity would benefit the development of new immunotherapies.