Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions
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 heterog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.565759/full |
| _version_ | 1819171686233145344 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xia Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T19:55:14Z |
| format | Article |
| id | doaj.art-54c4e4a0467a426faebcf1c097937748 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T19:55:14Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-54c4e4a0467a426faebcf1c0979377482022-12-21T18:14:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.565759565759Intratumor Heterogeneity of HLA-G Expression in Cancer LesionsXia Zhang0Aifen Lin1Qiu-Yue Han2Jian-Gang Zhang3Qiong-Yuan Chen4Yao-Han Ye5Wen-Jun Zhou6Hui-Hui Xu7Jun Gan8Wei-Hua Yan9Biological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaBiological Resource Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaMedical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaMedical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaMedical Research Center, TaiZhou Hospital of Zhejiang Province, Taizhou Enze Medical Center (Group), LinHai, ChinaSignaling 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.565759/fullHLA-Gtumorheterogeneityisoformantibodycolorectal cancer |
| spellingShingle | 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 Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions Frontiers in Immunology HLA-G tumor heterogeneity isoform antibody colorectal cancer |
| title | Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions |
| title_full | Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions |
| title_fullStr | Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions |
| title_full_unstemmed | Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions |
| title_short | Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions |
| title_sort | intratumor heterogeneity of hla g expression in cancer lesions |
| topic | HLA-G tumor heterogeneity isoform antibody colorectal cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.565759/full |
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