Nat Rev Cancer: Immune cell metabolism in cancer.

Through checkpoint blocking and the success of step-by-cell therapy, immunotherapy has become an exact cancer treatment model.
cell metabolism has become a key determinant of tumor cell and immune cell viability and function.
in order to maintain a huge anabolic demand, tumors use a special metabolism different from unconverted cells.
this metabolism leads to tumor microenvironments that are usually acidic, oxygen-deprived and/or lack of immune cells needed for critical nutrients.
in this case, tumor metabolism itself is a checkpoint that limits immune-mediated tumor destruction.
although metabolic processes may seem to be the basis of cancer and immune cells, metabolic heterogeneity and plasticity may help distinguish between the two.
in recent years, researchers have gradually discovered the metabolic processes between cancer cells and immune cells, as well as fundamental differences between different immune cells.
understanding these differences can reveal specific metabolic weaknesses, so new targets for treatments are designed to metabolize reprogramming to strengthen cancer immunotherapy.
Professor Jonathan D. Powell of the Sidney Kimmel Comprehensive Cancer Research Center at Johns Hopkins University School of Medicine in the United States published a review entitled "Metabolism of immune cells in cancer" in the journal Nat Rev Cancer (IF: 53.03).
understanding the different metabolic needs of the different cells that make up the immune response to cancer providean opportunities for selective regulation of immune cell function.
this subtle assessment of cancer and immune metabolism can reveal metabolic weaknesses and treatment windows with a view to intervening in enhanced immunotherapy.
the metabolism of metabolic adaptive immunosuppressive inhibition that cancer immunity evades.
immunosuppressive Treg cells are prioritized for tCA cycling and mitochondrial respiration.
While preliminary studies have shown that Treg cells' dependence on FAO does not take into account the off-target effect of etomoxir, other studies have shown that, although not the only way, FAO does support OXPHOS in Treg cells.
compared to Teff cells, Treg cells have lower in vitro glucose intake and glut1 expression levels are lower. Interestingly
, although glycoenzyme seises do not appear to play a key role in Treg cell differentiation or long-term phenotype, the authors' lab reports on a highly active treg cell subgroup called Effect Treg cells, which rely on the rise of glycoenzyme to get the best function.
unique amino acid metabolism in TME can also have a profound effect on Treg cells.
IDO1 activation can strongly promote Treg cell differentiation in vitro, which appears to be secondary to tryptophan deficiency and the production of downstream metabolites such as kynurenine.
mitochondrial oxidation nutrients, including glucose, amino acids and fatty acids, generate energy for stationary, differentiated cells through the triamcinolistic acid (TCA) circulation and electron delivery chain (ETC) (an efficient way).
however, during periods of increased proliferation, such as immune activation or malignant transformation, an alternative pathway for cell uplift glucose metabolism, called aerobic glycosis.
although inefficient in the production of ATP, aerobic sugar enzymes allow for faster glucose metabolism, effective treatment of excess carbon and regeneration of NAD, while maintaining the anabolic process of mitochondriase activity.
the sugar-dissolved intermediates through other basic ways, such as the phosphate pathway, the monocarbon pathway and the biosynthesis of amino cosaccharine.
these pathways support cellular processes that are critical to high-proliferative cells, such as the synthesis of fatty acids and nucleic acids.
in the case of increased proliferation, the metabolic pathway of glutamine is also increased. In addition to providing carbon skeletons for the TCA cycle and maintaining amino acid, nucleic acid and fatty acid biosynthesis intermediates,
glutamine is also a major source of nitrogen for amino acid and nucleic acid synthesis.
these cells also raise a wide range of amino acid transporter proteins, and mainly through NADPH synthesis to maintain a strict control of the redox balance.
many cells in the tumor microenvironment (TME) express exoenzymes, such as pyridoxine 2, 3-dioxyenzyme (IDO), arginine 1 (ARG1) and CD73, which consume nutrients and increase immunosuppressive metabolites such as kynurenine and adenosine.
with the disorder of the microvascular system, these metabolic adaptations can have a profound effect on the metabolic composition of TME, leading to the consumption of important nutrients, hypoxia, acidosis and the production of immunotoxic metabolites.
metabolism with congenital immunosuppressiveness.
TAMs can use highly immunosuppressive phenotypes.
it is useful to detect metabolic reprogramming that has been identified as M2 anti-inflammatory macrophages subgroups, characterized by immunosuppressive TAMs.
like Treg cells, M2 macrophages raise FAO and mitochondrial breathing.
M2 macrophages metabolize amino acids in a way different from inflammatory macrophages, expressing high levels of arginine 1 (ARG1), which consumes arginine and produces polyamines, which are important media for wound healing, but also have a high immunosuppressive effect.
another group of tumor-related immunosuppressive innate cells, MDSCs, appear to have a high metabolic activity.
the tumor-related MDSCs had an increase in oxycodone enzymes and OXPHOS in The Exosome.
the metabolic environment of TME is a reflection of the reprogramming of cancer metabolism.
nutritional deficiencies, hypoxia and toxic metabolites are conditions within TME that fight and affect the metabolism and function of T cells.
the consequences of TME status on immune cell responsecant edited by a growing body of preclinical, translational, and clinical studies.
develop differential metabolic plasticity Although the activation, proliferation, and function of Teff cells can be reduced by inhibiting many metabolic pathways, other properties, such as long-term viability or effect function after restimulation, may be enhanced.
although 2-DG inhibits the metabolism of glycoenzyme seisthing to inhibit the production of Teff cells, it also makes T-cells toward saperon, memory-like phenotypes.
interesting, blocking glycoenzyme during in vitro activation and amplification of T cells, and then infusion to tumor therapy, not only increases the survival of anti-tumor T cells, but also improves cytokine production and cytotoxicity.
a similar phenomenon is found in the response of AKT inhibition, glutamine blocking, hypoxia, arginine supplementation and potassium supplementation in CD8 plus Teff cells.
it may have different effects on cancer and immune response.
, for example, in the glucose-restricted CD8 plus Teff cells, acetic acid metabolism can save the function of T cells. it is significant
checkpoint blocking and immune metabolism to determine the metabolic outcomes and reactions of checkpoint treatment.
in some studies, checkpoint signals have been shown to regulate metabolism.
for example, the expression of PDL1 on tumor cells can drive the activation and glycoenzyme of Akt-mTOR, increase glucose intake, and increase the competition of T cells for glucose.
Cd155-TIGIT signaling from T cells in human stomach cancer tissue inhibited glucose intake, lactic acid production, and expression of glutase GLUT1 and HK2.
, on the contrary, the exagogication of the collaborative stimulation pathway GITR significantly improved the metabolic activity and proliferation of T cells compared with the control T cells of the same treatment.
target tumor metabolism by inhibiting glutamine metabolism in mouse models, thereby inhibiting tumor growth and making TME more suitable for antitumor-effect cells.
In addition, reprogramming T cells through metabolism to make them stronger and longer lasting memory cells may improve their response to checkpoint inhibitors.
recent clinical trials have demonstrated the combination of anti-folic acid permeitus and anti-PDL1 immune checkpoint blocking. in addition to having a direct anti-tumor effect,
permeyceus treatment can also enhance the metabolic adaptation and effect function of anti-tumor CD8 plus T cells, and induce the death of immune cells in cancer cells, triggering an immune response.
using small molecules, monoclonal antibodies, and genetic editing, metabolic processes can target cancer failure and inhibit immune cell metabolism, or, conversely, participate in and support effect cell metabolism.
inhibits the metabolic processes of immune populations and cancer cells can directly target metabolic pathways that reduce activity, as well as inactivation to consume nutrients (e.g. ARG1, IDO), resulting in toxic metabolites (e.g. lactic acid and CD73) or the number of effective cells that induce metabolic control (e.g. R-2-HG's mutant 1 subgeneration).
metabolic interventions can also induce beneficial changes in the effect subgroup, such as extended life span and antigen-specific immune memory.
conclusions and outlookSize Although most of the basis of immune metabolism has been communicated by the observation of cancer metabolism, it is clear that there is a clear difference between cancer and immunometabolic reprogramming.
these differences provide an opportunity for targeted metabolism as a means of increasing the effectiveness of immunotherapy.
this approach can be implemented through many different strategies.
include targeting tumor metabolism procedures to inhibit growth and alter TME, targeting inhibits the metabolism of immune cells to inhibit their function, and targeting the metabolism of targeted effect cells to enhance the effects of killer tumors.
future work should begin to focus on the metabolic interdependence of immune cells and cancer cells in TME.
in addition to nutrient consumption and the production of metabolites that inhibit the immune response to a certain extent, cancer cells in TME can participate in metabolic crosstalk with other cells, where metabolic procedures can induce and promote malignant progression.
reported that pancreatic astrocytes can provide alanine to cancer cells, thereby promoting the proliferation of cancer cells, and bone marrow matrix cells have been reported to provide cysteine to promote the survival of chronic lymphocytic leukemia cells.
in a separate report, ammonia from the metabolism of glutamine in cancer cells spreads through TME and triggers autophagy of cancer-related fibroblasts, which in turn provide protein breakdown products such as glutamine itself to further promote cancer cell metabolism.
it is important to understand whether and through what mechanisms immune-free cancers may be related to the metabolic mechanisms of immune cells and benefit from their remarkable metabolic flexibility.
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