Writing 丨 Wang Cong
Edit 丨 Wang Duoyu
WaterwritingCD8+T cells is anti- Key media of immune, but in Tumor micro-environment After the T cell receptor (TCR) in TME) is continuously stimulated, CD8+T cells will enter a state of dysfunction, which is the so -called T cell depletion (T Cell Exhaustion), which will lead to tumor immunityescape.The characteristic of exhausted T cells (TEX) is that the self-update ability decreases, the effect of effect cytokine (such as IL-2, TNF) is produced, and the production of co-inhibitors (such as PD-1, CTLA-4, TIM3, and LAG3) is produced.Relding.
Although the continuous TCR stimulus may be the main driving factor of T cell depletion, the metabolic pressure in the tumor microe environment (TME) can also promote the dysfunction of TEX cells.The rapid splitting of cancer cells leads to insufficient oxygen supply, resulting in hypoxia for tumor micro -environment, and promoting T -cell depletion.Cancer cells secrete a large number of metabolic by -products. Among them, lactic acid is one of the richest metabolites in the tumor microe environment, which will cause extracellular pH to decrease and inhibit T cell function.
Therefore, the metabolic driver of the CD8+TEX cell dysfunction that understands tumor infiltration is critical to the development of cancer treatment.
On November 8, 2024, researchers at University of Pittsburg published questions on Nature sub -magazines Nature Immunology For: Dysfunction of Exhausted T Cells is Enforced by Mct11-Mediated Lactate Metabolism.
This study found that the exhausted T cell (TEX) high -expression soluble carrier (SLC) protein MCT11 is promoted to promote lactic acid ~-------------------------------Img#5->
