Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions.

Abstract

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.

• Authors: Xia Zhang, Aifen Lin, Qiu-Yue Han, Jian-Gang Zhang, Qiong-Yuan Chen, Yao-Han Ye, Wen-Jun Zhou, Hui-Hui Xu, Jun Gan, Wei-Hua Yan
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 565759 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33329527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Zhang, Lin, Han, Zhang, Chen, Ye, Zhou, Xu, Gan and Yan.

Chemical References

• HLA-G Antigens

Topics

• Aged
• Aged, 80 and over
• Colorectal Neoplasms (immunology)
• Esophageal Neoplasms (immunology)
• Female
• HLA-G Antigens (immunology)
• Humans
• Male
• Middle Aged