Metabolic Modulation of the Tumor Microenvironment Leads to Multiple Checkpoint Inhibition and Immune Cell Infiltration

Kolb, David A.; Kolishetti, Nagesh; Surnar, Bapurao; Sarkar, Shrita; Guin, Subham; Shah, Anuj S.; Dhar, Shanta

doi:10.1021/acsnano.9b10037

Cited by 94 publications

(89 citation statements)

References 50 publications

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“…Metabolic transitions are not unique to cancer cells, but are also characteristic of other rapidly proliferating cells, such as activated T cells, Treg cell, neutrophils and so on [28]. Glucose is the nutrient that tumor cells absorb and consume the most, and is the most dependent, and it is also an important energy substance necessary for immune cell activation, differentiation, and function [51,52]. The tumor microenvironment (TME) is accompanied by different degrees and types of immune cell infiltration.…”

Section: Competition For Nutrients Between Tumor Cells and Immune Cellsmentioning

confidence: 99%

The cancer metabolic reprogramming and immune response

et al. 2021

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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.

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Section: Competition For Nutrients Between Tumor Cells and Immune Cellsmentioning

confidence: 99%

The cancer metabolic reprogramming and immune response

et al. 2021

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“…Alterations of the tumor microenvironment may result in the secretion of cytokines and activate various cell signaling pathways, thereby promoting tumor development. Tumor-infiltrating immune cells, including tumor-associated macrophages, dendritic cells, and lymphocytes, are the major components of the tumor microenvironment and important factors involved in the development of tumors (30).…”

Section: Discussionmentioning

confidence: 99%

The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

Chen

et al. 2021

Front. Oncol.

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Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

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“…(2) Targeting ROS and reactive nitrogen species (RNS). Mitochondria play an important role in CSC resistance to cytotoxic drugs or radiotherapy [ 161 ]. The whole mitochondrial cycle, from its biogenesis to mitophagy or apoptosis can be targeted to reduce mitochondrial fitness in cancer.…”

Section: Mitochondria Serving For Cancer: Metabolic Dysregulationmentioning

confidence: 99%

“…The whole mitochondrial cycle, from its biogenesis to mitophagy or apoptosis can be targeted to reduce mitochondrial fitness in cancer. Two elements are usually boosted, namely an augmentation of RNS and ROS and activation of the intrinsic apoptotic pathway [ 160 , 161 ].…”

Section: Mitochondria Serving For Cancer: Metabolic Dysregulationmentioning

confidence: 99%

“…Immune checkpoint inhibitor (ICI) therapy has opened a new strategy to treat cancer. Much further research is required for better understanding the immune ecosystem under ICI therapy, for proper adjuvants and dose calculation to increase desired responses and reducing severe adverse events [ 161 , 162 ]. Cancer vaccines and oncolytic viruses (OVs) exert much lower side effects than other systemic therapies, including ICI [ 163 ].…”

Section: Mitochondria Serving For Cancer: Metabolic Dysregulationmentioning

confidence: 99%

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Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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Metabolic Modulation of the Tumor Microenvironment Leads to Multiple Checkpoint Inhibition and Immune Cell Infiltration

Cited by 94 publications

References 50 publications

The cancer metabolic reprogramming and immune response

The cancer metabolic reprogramming and immune response

The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

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