{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:07:45Z","timestamp":1792123665400,"version":"4.4.0"},"reference-count":217,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472891"],"award-info":[{"award-number":["82472891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up\u2010regulated expression of co\u2010inhibitory receptors, including programmed death\u20101 (PD\u20101), cytotoxic T lymphocyte\u2010associated antigen\u20104 (CTLA\u20104), lymphocyte\u2010activation gene 3 (LAG\u20103), T cell immunoglobulin and mucin domain 3 (TIM\u20103) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibitors (ICIs) in reversing T cell exhaustion while delving into the complex molecular processes and functional works of these important co\u2010inhibitory receptors in tumourigenesis. Additionally, we examine the synergistic effects of combining ICIs with other therapeutic strategies, which can enhance anti\u2010tumour efficacy. Finally, the clinical implications of bispecific antibodies are highlighted, representing a promising frontier in cancer immunotherapy, that could revolutionise treatment paradigms while improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This review discusses five major co\u2010inhibitory receptors (PD\u20101, CTLA\u20104, LAG\u20103, TIM\u20103 and TIGIT) and their related mechanisms of T cell exhaustion in the tumour environment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We also discuss the clinical application of checkpoint inhibitors (ICIs) in cancer immunotherapy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The potential of bispecific antibodies (BsAbs) in cancer immunotherapy is highlighted.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70345","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T02:49:41Z","timestamp":1748227781000},"source":"Crossref","is-referenced-by-count":28,"title":["Unravelling T cell exhaustion through co\u2010inhibitory receptors and its transformative role in cancer immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Simin","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology, Women's Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 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