Elevated lactate dehydrogenase (LDH) can be a marker of immune suppression in cancer: Interplay between hematologic and solid neoplastic clones and their microenvironments

Article type: Research Article

Authors: Ding, Jennifer^a | Karp, Judith E.^b | Emadi, Ashkan^{a; *}

Affiliations: [a] Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA | [b] Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, MD, USA

Correspondence: [*] Corresponding author: Ashkan Emadi, University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, 22 South Greene Street, Room N9E24, Baltimore 21201, MD, USA. Tel.: +1 410 328 2596; Fax: +1 410 328 6896; E-mail: [email protected].

Abstract: Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment. LDH-A alters the tumor microenvironment via increased production of lactate. This leads to enhancement of immune-suppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells (DCs); and inhibition of cytolytic cells, such as natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs). By promoting immune-suppression in the tumor microenvironment, LDH-A is able to promote resistance to chemo/radio/targeted therapy. Here we discuss the evidence that LDH is both a metabolic and an immune surveillance prognostic biomarker and its elevation is harbinger of negative outcome in both solid and hematologic neoplasms.

Keywords: LDH (lactate dehydrogenase), cancer metabolism biomarker, cancer immune surveillance biomarker

DOI: 10.3233/CBM-160336

Journal: Cancer Biomarkers, vol. 19, no. 4, pp. 353-363, 2017