PMID- 35533264
OWN - NLM
STAT- MEDLINE
DCOM- 20220808
LR  - 20230206
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 20
IP  - 8
DP  - 2022 Aug 5
TI  - Pan-Cancer HLA Gene-Mediated Tumor Immunogenicity and Immune Evasion.
PG  - 1272-1283
LID - 10.1158/1541-7786.MCR-21-0886 [doi]
AB  - Human leukocyte antigen (HLA) expression contributes to the activation of 
      antitumor immunity through interactions with T-cell receptors. Pan-cancer 
      HLA-mediated immunogenicity and immunoediting mechanisms have not been 
      systematically studied previously. In a retrospective analysis of 33 tumor types 
      from the Cancer Genome Atlas (TCGA), we characterized the differential expression 
      of HLA class I and class II genes across various oncogenic pathways and immune 
      subtypes. While HLA I genes were upregulated in all immunogenically hot tumors, 
      HLA II genes were upregulated in an inflammatory immune subtype associated with 
      best prognosis and were systematically downregulated in specific oncogenic 
      pathways. A subset of immunogenically hot tumors which upregulated HLA class I 
      but not class II genes exploited HLA-mediated escape strategies. Furthermore, 
      with a machine learning model, we demonstrated that HLA gene expression data can 
      be used to predict the immune subtypes of patients receiving immune checkpoint 
      blockade and stratify patient survival. Interestingly, tumors with the highest 
      immune infiltration did not have the best prognosis but showed significantly 
      higher immune exhaustion. IMPLICATIONS: Taken together, we highlight the 
      prognostic potential of HLA genes in immunotherapies and suggest that higher 
      tumor immunogenicity mediated by HLA expression may sometimes lead to tumor 
      escape under strong selective pressure.
CI  - (c)2022 American Association for Cancer Research.
FAU - Gong, Xutong
AU  - Gong X
AD  - Department of Biomedical Engineering, Johns Hopkins University, Baltimore, 
      Maryland.
AD  - Institute for Computational Medicine, Johns Hopkins University, Baltimore, 
      Maryland.
FAU - Karchin, Rachel
AU  - Karchin R
AUID- ORCID: 0000-0002-5069-1239
AD  - Department of Biomedical Engineering, Johns Hopkins University, Baltimore, 
      Maryland.
AD  - Institute for Computational Medicine, Johns Hopkins University, Baltimore, 
      Maryland.
AD  - Department of Oncology, Johns Hopkins Medicine, Baltimore, Maryland.
LA  - eng
GR  - R01 CA121113/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - *Histocompatibility Antigens Class I/genetics
MH  - Humans
MH  - Immunotherapy
MH  - *Neoplasms/genetics/immunology
MH  - Retrospective Studies
MH  - *Tumor Escape
PMC - PMC9357147
MID - NIHMS1807268
COIS- Conflict of Interest The authors declare that there is no conflict of interest.
EDAT- 2022/05/10 06:00
MHDA- 2022/08/09 06:00
PMCR- 2023/02/05
CRDT- 2022/05/09 15:02
PHST- 2021/10/20 00:00 [received]
PHST- 2022/02/16 00:00 [revised]
PHST- 2022/04/29 00:00 [accepted]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/08/09 06:00 [medline]
PHST- 2022/05/09 15:02 [entrez]
PHST- 2023/02/05 00:00 [pmc-release]
AID - 707199 [pii]
AID - 10.1158/1541-7786.MCR-21-0886 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2022 Aug 5;20(8):1272-1283. doi: 10.1158/1541-7786.MCR-21-0886.