Ge Gao, Hao Wang, Rafeezul Mohamed, Yinming Liang
T cell exhaustion is a state of progressive functional impairment that occurs upon persistent antigenic stimulation and is a key mechanism by which chronic parasitic infections evade host immunity. As research into T cell exhaustion continues to deepen, immunotherapies targeting exhausted T cells have emerged as a prominent area of interest, particularly in cancers and chronic viral infections. However, T cell exhaustion caused by parasitic infections exhibits significant differences from classic T cell exhaustion observed in chronic viral infections, and understanding how parasites with their complex life cycles and unique immune evasion strategies, drive or modulate T cell exhaustion will be essential for developing targeted therapeutic approaches for diverse diseases. Therefore, this review summarizes the current understanding of mechanisms and research progress regarding T cell exhaustion in the context of chronic infections, with a specific focus on parasitic infections and their different developmental changes, meanwhile raises several key questions which still remain unanswered, aiming to provide insights and references for immunotherapy development in related diseases.