腫瘤微環境的代謝調控決定T細胞的分化及功能

Metabolic Modulators in the Tumor Microenvironment: Shaping T Cell Destiny and Functionality

腫瘤微環境是由癌細胞及其周圍非癌細胞和細胞外基質所構成的一個高度複雜的生物系統。本文深入探討了腫瘤微環境中代謝產物對癌細胞和免疫細胞行為的影響，尤其是對T細胞功能和分化的作用。癌細胞在腫瘤微環境中調整其代謝途徑，以支持其快速增殖並透過分泌乳酸和色氨酸代謝物等代謝產物來調控免疫細胞功能，從而促進免疫逃逸。乳酸的積累導致微環境酸化，抑制T細胞活動，而色氨酸代謝物通過激活特定受體來抑制效應T細胞的毒殺功能。本文還指出腫瘤微環境中的低氧狀態會激活HIF-1α等轉錄因子，增強癌細胞對葡萄糖的攝取和利用，促進血管新生，為腫瘤生長提供必要的營養。此外，癌細胞還可透過調節代謝酵素的表現來滿足其生物合成需求，例如增加脂肪酸合成。總結來說，深入了解腫瘤微環境中的代謝動態對於開發新的癌症治療策略至關重要。未來的治療方案可能會針對特定的代謝途徑，以恢復免疫系統的反應性並抑制癌細胞的增長。

The tumor microenvironment (TME) is a highly complex biological system composed of cancer cells, adjacent non-malignant cells, and the extracellular matrix. This review explores the impact of metabolic byproducts within the TME on the behavior of both cancer and immune cells, with a particular focus on the function and differentiation of T cells. Cancer cells adjust their metabolic pathways within the tumor microenvironment to support rapid proliferation and regulate immune cell function by secreting metabolic products such as lactic acid and tryptophan metabolites, thereby promoting immune evasion. The accumulation of lactic acid leads to acidification of the microenvironment, inhibiting T cell activity, while tryptophan metabolites suppress the cytotoxic function of effector T cells by activating specific receptors.Furthermore, the review underscores the role of hypoxic conditions in the TME in activating transcription factors like HIF-1α, which augments cancer cell glucose consumption and utilization, thereby promoting angiogenesis, and providing necessary nutrients for tumor growth. Additionally, cancer cells can meet their biosynthetic needs by regulating the expression of metabolic enzymes, including those involved in fatty acid synthesis. In conclusion, a comprehensive understanding of the metabolic interplay within the TME is vital for the innovation of novel cancer therapies. Prospective treatment modalities may target specific metabolic routes to restore the reactivity of the immune system and inhibit the growth of cancer cells.