Ding Jennifer, Karp Judith E, Emadi Ashkan
Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, MD, USA.
Cancer Biomark. 2017 Jul 4;19(4):353-363. doi: 10.3233/CBM-160336.
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.
肿瘤细胞的代谢转向高葡萄糖摄取和增强乳酸生成。乳酸脱氢酶（LDH）由两个主要亚基LDH - A和LDH - B组成，可逆地催化丙酮酸向乳酸或乳酸向丙酮酸的转化。LDH - A对丙酮酸具有更高的亲和力，是糖酵解途径中的关键酶。LDH升高是一种负面预后生物标志物，不仅因为它是参与癌症代谢的关键酶，还因为它使肿瘤细胞能够通过改变肿瘤微环境来抑制和逃避免疫系统。LDH - A通过增加乳酸生成来改变肿瘤微环境。这导致免疫抑制细胞增加，如髓源性抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）和树突状细胞（DC）；并抑制细胞溶解细胞，如自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）。通过促进肿瘤微环境中的免疫抑制，LDH - A能够促进对化疗/放疗/靶向治疗的抗性。在此，我们讨论LDH既是一种代谢又是一种免疫监测预后生物标志物的证据，以及其升高是实体瘤和血液肿瘤不良结局的先兆。
