Biomol Ther.  2018 Jan;26(1):4-9. 10.4062/biomolther.2017.194.

Convergence of Cancer Metabolism and Immunity: an Overview

• Van Dang C
• Kim JW

• KMID: 2400809
• DOI: http://doi.org/10.4062/biomolther.2017.194

Abstract

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Keyword

Cancer; Metabolism; Tumor suppressor; Oncogenes; Immunometabolism

MeSH Terms

Biosynthetic Pathways
Carcinogenesis
Glucose
Glycolysis
Homeostasis
Kynurenine
Lactic Acid
Metabolism*
Oncogenes
Oxidation-Reduction
Oxygen
Proto-Oncogenes
Protons
Quality Control
T-Lymphocytes
Tumor Microenvironment
Yeasts
Glucose
Kynurenine
Lactic Acid
Oxygen
Protons