The cancer metabolic reprogramming and immune response

Qing Pan,Pin Yi,Shiming Tan,Shan Rao,Qianjin Liao,Yaqian Han,Lu Tang,Jinguan Lin,Yingrui Shi,Min Su,Nayiyuan Wu,Jiaxin Liang,Yanyan Tang,Xia Luo,Yujuan Zhou,Longzheng Xia,Linda Oyang,Hui Wang,Yiqing Yang

doi:10.1186/s12943-021-01316-8

Abstract

The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

Highlights

Metabolism involves a network of biochemical reactions that convert nutrients into small molecules called metabolites [1]
The innate immune system consists of different populations of immune cells, containing macrophages, neutrophils, monocytes, eosinophils, basophils, and natural killer cells, which are responsible for innate immunity against pathogens to maintain homeostasis of the host [9]
Conclusions targeting of cancer and/or immune cell metabolism can synergize with antitumor immunity

Summary

Introduction

Metabolism involves a network of biochemical reactions that convert nutrients into small molecules called metabolites [1] Through these conversions and the resulting metabolites, cells generate the energy, redox equivalents and macromolecules (including proteins, lipids, DNA and RNA) that they require to survive and sustain cellular functions [2]. Emerging evidence indicates that cancer cells are able to suppress anti-tumor immune response by competing for and depleting essential nutrients or otherwise reducing the metabolic fitness of tumor-infiltrating immune cells [7, 8]. Both the innate and adaptive immune systems have established roles in the host defense against cancers through various mechanisms, which are raising an unprecedented development of modern cancer immunotherapies. We will discuss this process from the following aspects

Main text

The effect of metabolic pathways on tumor immunity mTOR pathway

Findings

Conclusions