A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex
Immune checkpoint inhibitors (ICI) have made progress in the field of anticancer treatment, but a certain number of PD-L1 negative OSCC patients still have limited benefits from ICI immuno-therapy because of primary immune evasion due to immunodeficiency. However, in existing human OSCC cell lines,...
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/35 |
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| author | Xiaofeng Zheng Yanan Sun Yiwei Li Jiyuan Ma Yinan Lv Yaying Hu Yi Zhou Jiali Zhang |
| author_facet | Xiaofeng Zheng Yanan Sun Yiwei Li Jiyuan Ma Yinan Lv Yaying Hu Yi Zhou Jiali Zhang |
| author_sort | Xiaofeng Zheng |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICI) have made progress in the field of anticancer treatment, but a certain number of PD-L1 negative OSCC patients still have limited benefits from ICI immuno-therapy because of primary immune evasion due to immunodeficiency. However, in existing human OSCC cell lines, cell models that can be used to study immunodeficiency have not been reported. The objective of this study was to establish a PD-L1 negative OSCC cell line, profile whether the presence of mutated genes is associated with immune deficiency, and explore its influence on the immune recognition of CD8<sup>+</sup> T cells in vitro. Here, we established a novel tongue SCC cell line (WU-TSC-1), which escapes from immune recognition by antigen presentation defects. This cell line was from a female patient who lacked typical causative factors. The expression of PD-L1 was negative in the WU-TSC-1 primary tumor, transplanted tumor, cultured cells and lipopolysaccharide stimulation. Whole exome sequencing (WES) revealed that WU-TSC-1 harbored missense mutations, loss of copy number and structural variations in human leukocyte antigen (<i>HLA</i>) class I/II genes. The tumor mutation burden (TMB) score was high at 292.28. In addition, loss of heterozygosity at beta-2-microglobulin (<i>B2M</i>)—a component of all HLA class I complex allotypes—was detected. Compared with the commonly used OSCC cell lines, genetic alterations in HLA class I and B2M impeded the proteins’ translation and inhibited the activation and killing effect of CD8<sup>+</sup> T cells. In all, the WU-TSC-1 cell line is characterized by genetic variations and functional defects of the HLA class I complex, leading to escape from recognition by CD8<sup>+</sup> T cells. |
| first_indexed | 2024-03-11T10:06:26Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:06:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f69b3fbc219246418bbeb96bca8a88522023-11-16T15:05:12ZengMDPI AGCells2073-44092022-12-011213510.3390/cells12010035A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I ComplexXiaofeng Zheng0Yanan Sun1Yiwei Li2Jiyuan Ma3Yinan Lv4Yaying Hu5Yi Zhou6Jiali Zhang7The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, ChinaImmune checkpoint inhibitors (ICI) have made progress in the field of anticancer treatment, but a certain number of PD-L1 negative OSCC patients still have limited benefits from ICI immuno-therapy because of primary immune evasion due to immunodeficiency. However, in existing human OSCC cell lines, cell models that can be used to study immunodeficiency have not been reported. The objective of this study was to establish a PD-L1 negative OSCC cell line, profile whether the presence of mutated genes is associated with immune deficiency, and explore its influence on the immune recognition of CD8<sup>+</sup> T cells in vitro. Here, we established a novel tongue SCC cell line (WU-TSC-1), which escapes from immune recognition by antigen presentation defects. This cell line was from a female patient who lacked typical causative factors. The expression of PD-L1 was negative in the WU-TSC-1 primary tumor, transplanted tumor, cultured cells and lipopolysaccharide stimulation. Whole exome sequencing (WES) revealed that WU-TSC-1 harbored missense mutations, loss of copy number and structural variations in human leukocyte antigen (<i>HLA</i>) class I/II genes. The tumor mutation burden (TMB) score was high at 292.28. In addition, loss of heterozygosity at beta-2-microglobulin (<i>B2M</i>)—a component of all HLA class I complex allotypes—was detected. Compared with the commonly used OSCC cell lines, genetic alterations in HLA class I and B2M impeded the proteins’ translation and inhibited the activation and killing effect of CD8<sup>+</sup> T cells. In all, the WU-TSC-1 cell line is characterized by genetic variations and functional defects of the HLA class I complex, leading to escape from recognition by CD8<sup>+</sup> T cells.https://www.mdpi.com/2073-4409/12/1/35HLA class I complex<i>B2M</i>tongue squamous cell carcinomaimmune recognitionPD-L1 |
| spellingShingle | Xiaofeng Zheng Yanan Sun Yiwei Li Jiyuan Ma Yinan Lv Yaying Hu Yi Zhou Jiali Zhang A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex Cells HLA class I complex <i>B2M</i> tongue squamous cell carcinoma immune recognition PD-L1 |
| title | A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex |
| title_full | A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex |
| title_fullStr | A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex |
| title_full_unstemmed | A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex |
| title_short | A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in <i>HLA</i> Class I Complex |
| title_sort | novel tongue squamous cell carcinoma cell line escapes from immune recognition due to genetic alterations in i hla i class i complex |
| topic | HLA class I complex <i>B2M</i> tongue squamous cell carcinoma immune recognition PD-L1 |
| url | https://www.mdpi.com/2073-4409/12/1/35 |
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