PMID- 36611830 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230206 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 1 DP - 2022 Dec 22 TI - A Novel Tongue Squamous Cell Carcinoma Cell Line Escapes from Immune Recognition due to Genetic Alterations in HLA Class I Complex. LID - 10.3390/cells12010035 [doi] LID - 35 AB - 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(+) 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 (HLA) class I/II genes. The tumor mutation burden (TMB) score was high at 292.28. In addition, loss of heterozygosity at beta-2-microglobulin (B2M)-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(+) 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(+) T cells. FAU - Zheng, Xiaofeng AU - Zheng X AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Sun, Yanan AU - Sun Y AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Li, Yiwei AU - Li Y AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Ma, Jiyuan AU - Ma J AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Lv, Yinan AU - Lv Y AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Hu, Yaying AU - Hu Y AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. FAU - Zhou, Yi AU - Zhou Y AUID- ORCID: 0000-0001-9616-7283 AD - The 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, China. FAU - Zhang, Jiali AU - Zhang J AUID- ORCID: 0000-0003-0965-3027 AD - The 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, China. AD - Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221222 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (B7-H1 Antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) SB - IM MH - Humans MH - Female MH - CD8-Positive T-Lymphocytes MH - B7-H1 Antigen/metabolism MH - *Carcinoma, Squamous Cell/pathology MH - *Tongue Neoplasms/genetics MH - Histocompatibility Antigens Class I/metabolism MH - Mutation MH - HLA Antigens MH - Cell Line MH - Tongue/pathology PMC - PMC9818362 OTO - NOTNLM OT - B2M OT - HLA class I complex OT - PD-L1 OT - immune recognition OT - tongue squamous cell carcinoma COIS- The authors declare no conflict of interest. EDAT- 2023/01/09 06:00 MHDA- 2023/01/11 06:00 PMCR- 2022/12/22 CRDT- 2023/01/08 01:05 PHST- 2022/11/06 00:00 [received] PHST- 2022/12/16 00:00 [revised] PHST- 2022/12/19 00:00 [accepted] PHST- 2023/01/08 01:05 [entrez] PHST- 2023/01/09 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/12/22 00:00 [pmc-release] AID - cells12010035 [pii] AID - cells-12-00035 [pii] AID - 10.3390/cells12010035 [doi] PST - epublish SO - Cells. 2022 Dec 22;12(1):35. doi: 10.3390/cells12010035.