TY - JOUR
T1 - Lactate contribution to the tumor microenvironment
T2 - Mechanisms, effects on immune cells and therapeutic relevance
AU - Romero-Garcia, Susana
AU - Moreno-Altamirano, María Maximina B.
AU - Prado-Garcia, Heriberto
AU - Sánchez-García, Francisco Javier
N1 - Publisher Copyright:
© 2016 Romero-Garcia, Moreno-Altamirano, Prado-Garcia and Sánchez-García.
PY - 2016
Y1 - 2016
N2 - Malignant transformation of cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate, even under normoxic conditions; this phenomenon of aerobic glycolysis is largely known as the Warburg effect. This metabolic reprograming serves to generate biosynthetic precursors, thus facilitating the survival of rapidly proliferating malignant cells. Extracellular lactate directs the metabolic reprograming of tumor cells, thereby serving as an additional selective pressure. Besides tumor cells, stromal cells are another source of lactate production in the tumor microenvironment, whose role in both tumor growth and the antitumor immune response is the subject of intense research. In this review, we provide an integral perspective of the relationship between lactate and the overall tumor microenvironment, from lactate structure to metabolic pathways for its synthesis, receptors, signaling pathways, lactate-producing cells, lactate-responding cells, and how all contribute to the tumor outcome. We discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion and we explore the possibility of targeting lactate metabolism for cancer treatment, as well as of using lactate as a prognostic biomarker.
AB - Malignant transformation of cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate, even under normoxic conditions; this phenomenon of aerobic glycolysis is largely known as the Warburg effect. This metabolic reprograming serves to generate biosynthetic precursors, thus facilitating the survival of rapidly proliferating malignant cells. Extracellular lactate directs the metabolic reprograming of tumor cells, thereby serving as an additional selective pressure. Besides tumor cells, stromal cells are another source of lactate production in the tumor microenvironment, whose role in both tumor growth and the antitumor immune response is the subject of intense research. In this review, we provide an integral perspective of the relationship between lactate and the overall tumor microenvironment, from lactate structure to metabolic pathways for its synthesis, receptors, signaling pathways, lactate-producing cells, lactate-responding cells, and how all contribute to the tumor outcome. We discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion and we explore the possibility of targeting lactate metabolism for cancer treatment, as well as of using lactate as a prognostic biomarker.
KW - Immune escape
KW - L-lactate metabolism
KW - Monocarboxylate transporter
KW - Tumor microenvironment
KW - Warburg effect
UR - http://www.scopus.com/inward/record.url?scp=84962526021&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2016.00052
DO - 10.3389/fimmu.2016.00052
M3 - Artículo de revisión
C2 - 26909082
SN - 1664-3224
VL - 7
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - FEB
M1 - 52
ER -