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已发表论文
靶向 ILT4 以提高实体瘤免疫治疗效果：从实验室到临床
Received 18 June 2025
Accepted for publication 4 September 2025
Published 18 September 2025 Volume 2025:14 Pages 1073—1085
DOI https://doi.org/10.2147/ITT.S548082
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Michael Shurin
Aiqin Gao,1,* Shuyun Wang,2,* Yuping Sun2
1Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yuping Sun, Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, Shandong Province, 250117, People’s Republic of China, Tel +8613370582181, Email 13370582181@163.com
Abstract: Immunotherapy, especially immune checkpoint inhibitors (ICIs), has greatly changed the paradigm of cancer treatment in the past decade. However, the efficacy of ICIs in solid tumors is still limited. Even in patients with high PD-L1 expression, the response rate is less than 40%. The immunosuppressive tumour microenvironment (TME) represents a major cause of ICI hyporesponsiveness due to its inhibition on effective T-cell trafficking and immunity. Exploring novel immunotargets and developing combination therapeutics represent promising strategies to improve tumor response to immunotherapy. Immunoglobulin-like transcript (ILT) 4 is a classical inhibitory molecule in myeloid cells. Recently, ILT4 expression was discovered in tumour cells and multiple immunocytes in the TME, functionally inducing tumour growth, metastasis, and immune escape. Our group proposed ILT4 as a novel checkpoint molecule for tumour immunotherapy in 2018. In the past 5 years, translational research on ILT4 has made remarkable advances. Here, we update recent findings on ILT4 function in the TME, summarize the translational research on the development of therapeutic ILT4 antibodies, and highlight emerging clinical trial data supporting the role of ILT4 blockade in improving immunotherapy efficacy.
Keywords: ILT4, immunosuppression, translational research, clinical trials, immunotherapy
1Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yuping Sun, Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, Shandong Province, 250117, People’s Republic of China, Tel +8613370582181, Email 13370582181@163.com
Abstract: Immunotherapy, especially immune checkpoint inhibitors (ICIs), has greatly changed the paradigm of cancer treatment in the past decade. However, the efficacy of ICIs in solid tumors is still limited. Even in patients with high PD-L1 expression, the response rate is less than 40%. The immunosuppressive tumour microenvironment (TME) represents a major cause of ICI hyporesponsiveness due to its inhibition on effective T-cell trafficking and immunity. Exploring novel immunotargets and developing combination therapeutics represent promising strategies to improve tumor response to immunotherapy. Immunoglobulin-like transcript (ILT) 4 is a classical inhibitory molecule in myeloid cells. Recently, ILT4 expression was discovered in tumour cells and multiple immunocytes in the TME, functionally inducing tumour growth, metastasis, and immune escape. Our group proposed ILT4 as a novel checkpoint molecule for tumour immunotherapy in 2018. In the past 5 years, translational research on ILT4 has made remarkable advances. Here, we update recent findings on ILT4 function in the TME, summarize the translational research on the development of therapeutic ILT4 antibodies, and highlight emerging clinical trial data supporting the role of ILT4 blockade in improving immunotherapy efficacy.
Keywords: ILT4, immunosuppression, translational research, clinical trials, immunotherapy