Lipids for CD8+ TILs: Beneficial or harmful?

Abstract

Lipids and lipid metabolism play crucial roles in regulating T cell function and are tightly related to the establishment of immune memory. It is reported that tumor-infiltrating CD8⁺T lymphocytes (CD8⁺TILs) burn fats to restore their impaired effector function due to the lack of glucose. Conversely, fatty acids (FAs) and cholesterol in the tumor microenvironment (TME) drive the CD8⁺ TILs dysfunction. The origin of dysfunctional CD8⁺ TILs shares important features with memory T cell's precursor, but whether lipids and/or lipid metabolism reprogramming directly influence the memory plasticity of dysfunctional CD8⁺ TILs remains elusive. It is necessary to understand the interplay between cellular lipid metabolism and dysfunction of CD8⁺ TILs in the case of targeting T cell's metabolism to synergize cancer immunotherapy. Therefore, in this review, we summarize the latest research on CD8⁺ TILs lipid metabolism, evaluate the impacts of lipids in the TME to CD8⁺ TILs, and highlight the significance of promoting memory phenotype cell formation by targeting CD8⁺ T cells lipid metabolism to provide longer duration of cancer immunotherapy efficacy.

Keywords: CD8+ T cell; Exhausted T cell; cholesterol; fatty acid; fatty acid oxidation; metabolism; tumor microenvironment (TME).