Lipids for CD8(+) TILs: Beneficial or harmful?

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.