Effect of cellular metabolites on tumors

Tumors contain multiple cell types that interact with each other to form a unique network

The occurrence and development of tumors depends not only on genetic mutations, but also on the heterogeneity

Bidirectional regulation can occur between tumor cells and immune cells in TME, and tumor cells regulate the behavior of immune cells by secreting growth factors and cytokines; The interaction between tumor cells and immune cells can also break through the balance of the body's body, mobilize internal and external resources, create TME suitable for self-growth, and affect the response

Effects of metabolic reprogramming of tumor cells on tumors

Metabolic changes are a common feature of most cancer cells, and the first common biochemical changes that occur in cancer cells are abnormal

Glucose can also enter the pentose phosphoric acid or glycogenesis pathway to store carbon, and the metabolites produced support a variety of biological macromolecules synthesis, antioxidant production, and protein glycosylation pathways

Metabolic intermediates are thought to be important regulators of cell signaling and the epigenome

Effects of metabolic reprogramming of immune cells on tumors

The use of energy by immune cells during the quiescent and active phases also differs

Of particular note is that during T cell therapy, antigen-specific T cells or peripheral blood T cells transduced by chimeric antigen receptors are amplified in vitro and then transfused back to the patient, providing a way

Metabolic competition between tumor cells and immune cells

There is metabolic competition and metabolite-mediated communication
between tumor cells and various tumor invasive immune cells.

Tumor cells preferentially pass through the Warburg effect, which reduces glucose utilization and increases the abundance
of lactic acid in TME.

Glucose-deficient, lactate-rich TME impairs T cell function, thereby impairing the anti-tumor immune response and biasing tumor-associated macrophages toward the tumor-friendly M2-like phenotype
.

Competition for amino acids by T cells, tumor cells, and/or other cells in TME may also inhibit anti-tumor immunity, further inhibiting T cell activation and promoting the development
of Treg cells.

The availability and use of T cell fatty acids within TME is also affected
by competition with tumor cells.

It is important to note that the high rate of cholesterol esterification in tumors impairs the response of
T cells.

Therefore, disrupting the cholesterol esterification reaction by increasing the concentration of cholesterol in the plasma membrane of CD8+ T cells may promote the proliferation of CD8+ T cells and improve their effect function
.

▲Metabolic pathways in the tumor microenvironment and their effects on the function of anti-tumor immune cells (Image source: Reference source 1)

brief summary

Methods that target tumor cell or immune cell metabolism can work synergistically with immunotherapy, and utilizing metabolic pathways in TME may increase the lower response rates
of current immunotherapies.

Although various combinations of metabolites and immunotherapy have been used in clinical trials, many metabolism-related drugs still have great difficulties
in the development process.

Speculating on the key points of combined therapy with targeted metabolism and immunity in the future is mainly the following two: First, the cellular metabolic pathway is more complex, there are more bypasses, and the compensatory mechanism of these bypasses makes the metabolic inhibition effect poor, and more in-depth research is needed on the metabolism and signaling pathways of tumors; Secondly, in addition to the presence of macromolecular substances such as glucose, amino acids and lipids that are currently studied more, there are also a variety of microorganisms and trace metals, etc.
, which play an important role in the functional composition and activation of a variety of metabolic enzymes, and may also participate in metabolic cycles, play a role in signal transduction and other functions, and the future needs to conduct in-depth research and discussion
on the function of these trace elements in tumor cells and immune cells.

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