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Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response

 Min Hwan Kim  ;  Jae-Hwan Kim  ;  Ji Min Lee  ;  Jae Woo Choi  ;  Dongmin Jung  ;  Hojin Cho  ;  Hyundeok Kang  ;  Min Hee Hong  ;  Su Jin Heo  ;  Se Heon Kim  ;  Eun Chang Choi  ;  Da Hee Kim  ;  Young Min Park  ;  Sangwoo Kim  ;  Sun Och Yoon  ;  Yoon Woo Koh  ;  Byoung Chul Cho  ;  Hye Ryun Kim 
 BRITISH JOURNAL OF CANCER, Vol.122(11) : 1649-1660, 2020-04 
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Background: Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. Methods: We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. Results: All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-β signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). Conclusion: Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.
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1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koh, Yoon Woo(고윤우)
Kim, Min Hwan(김민환) ORCID logo https://orcid.org/0000-0002-1595-6342
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Kim, Se Heon(김세헌)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Young Min(박영민) ORCID logo https://orcid.org/0000-0002-7593-8461
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Choi, Eun Chang(최은창)
Heo, Su Jin(허수진) ORCID logo https://orcid.org/0000-0002-0615-5869
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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