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HLA-I-restricted CD8 + T cell immunity may accelerate tumorigenesis in conjunction with VHL inactivation

Authors
 BeumJin Park  ;  Seok-Jae Heo  ;  Yong Joon Lee  ;  Mi-Kyoung Seo  ;  Jiyun Hong  ;  Eui-Cheol Shin  ;  Inkyung Jung  ;  Sangwoo Kim 
Citation
 ISCIENCE, Vol.25(6) : 104467, 2022-06 
Journal Title
ISCIENCE
Issue Date
2022-06
Keywords
Cancer ; Components of the immune system ; Immunology
Abstract
CD8+ T cells recognize and kill tumor cells with HLA-I tumor antigens in early tumorigenesis, the efficiency of which differs according to antigen-recognition coverage, as shown in earlier tumor onset in HLA-I homozygosity. However, the universality of these associations remains unknown. Here, we assessed the tumor type and driver mutation specificity in the association between tumor onset age and HLA-I zygosity. Statistical analyses identified an unexpected negative relationship in tumors with VHL biallelic loss, wherein HLA-I heterozygosity was associated with earlier tumor onset, while all others showed either no or a positive association. Testing on an independent dataset reproduced the VHL-dependent acceleration of tumor onset in the HLA-I heterozygous group, confirming the association. Further speculation proposed VEGF-A-mediated T cell exhaustion under VHL inactivation as a potential mechanism. Our findings suggest that CD8+ T cell immunity in early tumor suppression can be conditional to the genetic status of tumors and may even lead to adverse consequences.
Files in This Item:
T202202950.pdf Download
DOI
10.1016/j.isci.2022.104467
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189547
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