PMID- 33329527 OWN - NLM STAT- MEDLINE DCOM- 20210517 LR - 20210517 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions. PG - 565759 LID - 10.3389/fimmu.2020.565759 [doi] LID - 565759 AB - 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. CI - Copyright (c) 2020 Zhang, Lin, Han, Zhang, Chen, Ye, Zhou, Xu, Gan and Yan. FAU - Zhang, Xia AU - Zhang X AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Lin, Aifen AU - Lin A AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Han, Qiu-Yue AU - Han QY AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Zhang, Jian-Gang AU - Zhang JG AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Chen, Qiong-Yuan AU - Chen QY AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Ye, Yao-Han AU - Ye YH AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Zhou, Wen-Jun AU - Zhou WJ AD - Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Xu, Hui-Hui AU - Xu HH AD - Medical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Gan, Jun AU - Gan J AD - Medical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. FAU - Yan, Wei-Hua AU - Yan WH AD - Medical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201119 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA-G Antigens) SB - IM MH - Aged MH - Aged, 80 and over MH - Colorectal Neoplasms/*immunology MH - Esophageal Neoplasms/*immunology MH - Female MH - HLA-G Antigens/*immunology MH - Humans MH - Male MH - Middle Aged PMC - PMC7717930 OTO - NOTNLM OT - HLA-G OT - antibody OT - colorectal cancer OT - esophageal cancer OT - heterogeneity OT - isoform OT - tumor EDAT- 2020/12/18 06:00 MHDA- 2021/05/18 06:00 PMCR- 2020/01/01 CRDT- 2020/12/17 05:50 PHST- 2020/06/03 00:00 [received] PHST- 2020/10/27 00:00 [accepted] PHST- 2020/12/17 05:50 [entrez] PHST- 2020/12/18 06:00 [pubmed] PHST- 2021/05/18 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.565759 [doi] PST - epublish SO - Front Immunol. 2020 Nov 19;11:565759. doi: 10.3389/fimmu.2020.565759. eCollection 2020.