The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger...The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.展开更多
基金supported by a CRI Lloyd J. Old STAR Award(Grant No. 3914)a Helmholtz Young Investigator Award(Grant No. VH-NG-1113)+7 种基金an EMBO Young Investigator Awardan Exploration Grant of the Boehringer Ingelheim Foundation (BIS)the German Research Foundation (DFG,Grant Nos. CU375/5-1, CU375/5-2, CU375/7-1, CU375/9-1, and 259332240/RTG2099)the German Cancer Aid Foundation (DKH, Grant Nos. 70113343 and 70114224)the Helmholtz Zukunftsthema Ageing and Metabolic Programming (AMPro, Grant No. ZT0026)HI-TRON KickStart Seed Funding (Grant No. HITR-2021-08)the Hector Foundation (Grant No. M20102)an ERC Consolidator Award (Grant No. 101045416)
文摘The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.
