HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges

Frontiers in Immunology

Wei-Hua Yan³  Aifen Lin³ 

[1] Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province, Linhai, China;Biological Resource Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China;;Key Laboratory of Minimally Invasive Techniques &

关键词: HLA-G;    immune checkpoint;    immune checkpoint inhibitor;    immunoglobulin-like transcript;    cancer immunotherapy;   

DOI  :  10.3389/fimmu.2021.698677

来源: DOAJ

【 摘 要 】

Immune checkpoint inhibitors (ICIs) have become a promising immunotherapy for cancers. Human leukocyte antigen-G (HLA-G), a neoantigen, its biological functions and clinical relevance have been extensively investigated in malignancies, and early clinical trials with “anti-HLA-G strategy” are being launched for advance solid cancer immunotherapy. The mechanism of HLA-G as a new ICI is that HLA-G can bind immune cell bearing inhibitory receptors, the immunoglobulin-like transcript (ILT)-2 and ILT-4. HLA-G/ILT-2/-4 (HLA-G/ILTs) signaling can drive comprehensive immune suppression, promote tumor growth and disease progression. Though clinical benefits could be expected with application of HLA-G antibodies to blockade the HLA-G/ILTs signaling in solid cancer immunotherapy, major challenges with the diversity of HLA-G isoforms, HLA-G/ILTs binding specificity, intra- and inter-tumor heterogeneity of HLA-G, lack of isoform-specific antibodies and validated assay protocols, which could dramatically affect the clinical efficacy. Clinical benefits of HLA-G-targeted solid cancer immunotherapy may be fluctuated or even premature unless major challenges are addressed.

【 授权许可】

Unknown