T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle
Wen-Ping Lin,
Hao Li,
Zhi-Jun Sun
Affiliations
Wen-Ping Lin
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, PR China
Hao Li
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, PR China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, PR China; Corresponding author. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, China.
Zhi-Jun Sun
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, PR China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, PR China; Corresponding author. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, 237 Luoyu Road, Wuhan, 430079, Hubei Province, China.
Summary: Immune therapies represented by immune checkpoint blockade (ICB) have significantly transformed cancer treatment. However, the effectiveness of these treatments depends on the status of T cells. T cell exhaustion, characterized by diminished effector function, increased expression of co-inhibitory receptors, and clonal deletion, emerges as a hypofunctional state resulting from chronic exposure to antigens, posing an obstacle to ICB therapy. Several studies have deeply explored T cell exhaustion, providing innovative insights and correlating T cell exhaustion with tertiary lymphoid structures (TLS) formation. TLS, lymphocyte aggregates formed in non-lymphoid tissues amid chronic inflammation, serve as pivotal reservoirs for anti-tumour immunity. Here, we underscore the pivotal role of T cell exhaustion as a signalling mechanism in reinvigorating anti-tumour immunity by turbocharging cancer-immunity (CI) cycle, particularly when tumour becomes unmanageable. Building upon this concept, we summarize emerging immunotherapeutic strategies aimed at enhancing the response rate to ICB therapy and improving patient prognosis.
