The cellular metabolic landscape in the tumor milieu regulates the activity of myeloid infiltrates

Abstract

Malignant cells upregulate distinct energy metabolism programs that support their proliferation, migration, and adaptation to the stressful tumor microenvironment (TME). Additionally, this exaggerated metabolic activity allows cancer cells to hijack essential nutrients and outcompete neighboring infiltrating immune cells, thereby impairing antitumor immunity. During recent years, there has been great interest in the field to understand the tumor-induced energy metabolism signals that regulate the function of immune cells in individuals with cancer. Accordingly, it is now well accepted that uncovering the mechanisms that instruct the metabolic behavior of cancer cells and tumor-associated immune cells is an indispensable strategy for the development of new approaches to overcome immune suppression in tumors. Thus, in this minireview, we briefly discuss the interaction between particular metabolic signaling pathways and immunosuppressive activity in different subsets of myeloid cells within the TME. Additionally, we illustrate potential central mechanisms controlling the metabolic reprogramming of myeloid cells in response to tumor-derived factors.

Scinderin suppresses cell proliferation and predicts the poor prognosis of hepatocellular carcinoma

“…Hasmim et al (15) demonstrated the weak expression of SCIN in 9 out of 83 patients with head and neck cancer, indicating that the role of SCIN may vary within different types of tumor. This paradoxical function of SCIN in different types of cancer may be attributed to different genetic backgrounds and distinct tumor milieu(22). However, the present study demonstrated that SCIN was tumor suppressive in HCC.…”

Turn Back the TIMe: Targeting Tumor Infiltrating Myeloid Cells to Revert Cancer Progression

“…Moreover glycolysis, the metabolic pathway preferred by TIMs and tumor cells during the elimination phase, mediates production of proteins, nucleic acids, lipids, lactate, adenosine, and consequently immunosuppressive acidification of the TME. As a result TIMs undergo peroxisome proliferator-activated receptor gamma (PPARγ) and STAT-mediated metabolic reprogramming ( 61 ). They switch from glycolysis to oxidative phosphorylation and lipid catabolism (fatty acid oxidation).…”

Mechanistic insights into cancer immunity and immunotherapy

“…Accordingly, there has been a surge of interest in defining the mechanisms by which aberrant immune cell metabolism impacts cancer progression and therapeutic outcomes. In this issue, Rodriguez and Peng discuss the latest research advances in cancer immunometabolism and how novel insights can be harnessed to treat cancer 7,8 . Myeloid cells contribute to the suppressive intratumoral environment and may directly promote human tumor stemness 9 .…”

“…Myeloid cells contribute to the suppressive intratumoral environment and may directly promote human tumor stemness 9 . Tumorinfiltrating myeloid cells are the subject of a review by Rodriguez 7 . These heterogeneous and developmentally immature myeloid cells are responsive to dysfunctional metabolism such as poor glycolysis and enhanced lipid metabolism and the associated metabolites, such as adenosine, cAMP, IDO, lactate, succinate, PGE2, fatty acid, lipoproteins, and oxidized forms that may promote their intratumoral accumulation and suppressive effects on T cells 7,8 .…”

“…Tumorinfiltrating myeloid cells are the subject of a review by Rodriguez 7 . These heterogeneous and developmentally immature myeloid cells are responsive to dysfunctional metabolism such as poor glycolysis and enhanced lipid metabolism and the associated metabolites, such as adenosine, cAMP, IDO, lactate, succinate, PGE2, fatty acid, lipoproteins, and oxidized forms that may promote their intratumoral accumulation and suppressive effects on T cells 7,8 . In the review by Peng and colleagues, in addition to discussing the tumor-associated metabolites and myeloid cells, they emphasize that abnormal metabolism impacts the phenotype and function of naive T cells, effector T cells, and regulatory T cells.…”