Browse
Submit Data
Databases
API
Help

Dataset Information

3 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lactate dehydrogenase: a marker of diminished antitumor immunity.

ABSTRACT: Lactate dehydrogenase (LDH) levels are inversely related with response to checkpoint inhibitors. Elevated LDH levels are the product of enhanced glycolytic activity of the tumor and tumor necrosis due to hypoxia, the latter being associated with high tumor burden. In this review, we elucidate the effects of glycolysis and hypoxia on antitumor immunity and set forth ways to improve response to immunotherapy in cancer patients with elevated LDH levels. We discuss the current knowledge on combining immunotherapy with glycolysis inhibitors, anti-acidifying drugs, anti-angiogenic or cytoreductive therapy.

SUBMITTER: Van Wilpe S

PROVIDER: S-EPMC7051189 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity.

Project description: Not available

| S-EPMC5505499 | biostudies-literature

Lactate dehydrogenase inhibition synergizes with IL-21 to promote CD8+ T cell stemness and antitumor immunity.

Project description: Not available

| S-EPMC7084161 | biostudies-literature

Lactate dehydrogenase inhibition synergizes with IL-21 to promote CD8+ T cell stemness and antitumor immunity

Project description:Interleukin (IL)-2 and IL-21 dichotomously shape CD8+ T cell differentiation. IL-2 drives terminal differentiation, generating cells that are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (TSCM) and antitumor responses. Here we investigated the role of metabolic programming in the developmental differences induced by these cytokines. IL-2 promoted effector-like metabolism and aerobic glycolysis, robustly inducing lactate dehydrogenase (LDH) and lactate production, whereas IL-21 maintained a metabolically quiescent state dependent on oxidative phosphorylation. LDH inhibition rewired IL-2–induced effects, promoting pyruvate entry into the tricarboxylic acid cycle and inhibiting terminal effector and exhaustion programs, including mRNA expression of members of the NR4A family of nuclear receptors, as well as Prdm1 and Xbp1. While deletion of Ldha prevented development of cells with antitumor effector function, transient LDH inhibition enhanced the generation of memory cells capable of triggering robust antitumor responses after adoptive transfer. LDH inhibition did not significantly affect IL-21–induced metabolism but caused major transcriptomic changes, including the suppression of IL-21–induced exhaustion markers LAG3, PD1, 2B4, and TIM3. LDH inhibition combined with IL-21 increased the formation of TSCM cells, resulting in more profound antitumor responses and prolonged host survival. These findings indicate a pivotal role for LDH in modulating cytokine-mediated T cell differentiation and underscore the therapeutic potential of transiently inhibiting LDH during adoptive T cell-based immunotherapy, with an unanticipated cooperative antitumor effect of LDH inhibition and IL-21.

2020-02-13 | GSE143903 | GEO

Lactate dehydrogenase level as a COVID-19 severity marker.

Project description: Not available

| S-EPMC7666711 | biostudies-literature

Sepsis-Induced State of Immunoparalysis Is Defined by Diminished CD8 T Cell-Mediated Antitumor Immunity.

Project description: Not available

| S-EPMC6650357 | biostudies-literature

Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer.

Project description: Not available

| S-EPMC3727144 | biostudies-literature

Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase.

Project description: Not available