Research progress of T cell anti-tumor function regulated by endoplasmic reticulum stress

Endoplasmic reticulum (ER) stress is involved in the development and progression of tumors.In recent years, great attention has been paid to the study of the interplay of ER stress and T cell differentiation and functionality.Intense ER stress in the tumor-infiltrating T cells exacerbates T cell exhaustion and impairs T cell anti-tumor immunity.Therefore, a variety of ER stress inhibitors have been developed and utilized to alleviate T cell exhaustion, which improves T cell function in tumor microenvironment.Furthermore, the downregulation of several circadian clock genes like Per1 and Per2 also aggravates T cell exhaustion, and the key downstream effector molecules in ER stress regulate the transcription of Per family, thus enhancing the T cell function.In the present manuscript, we particularly summarize how ER stress impacts the anti-tumor immunity of T cells, and further discuss potential strategies for improving tumor immunotherapy via targeting ER stress.