Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response
| Autor: | Min Hwan Kim, Hyundeok Kang, Sangwoo Kim, Hojin Cho, Eun Chang Choi, Se-Heon Kim, Su Jin Heo, Young Min Park, Da Hee Kim, Jae Hwan Kim, Min Hee Hong, Sun Och Yoon, Hye Ryun Kim, Ji Min Lee, Yoon Woo Koh, Dongmin Jung, Byoung Chul Cho, Jae Woo Choi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer microenvironment
Cancer Research T cell medicine.medical_treatment Biology Article 03 medical and health sciences 0302 clinical medicine Immune system Lymphocytes Tumor-Infiltrating Downregulation and upregulation medicine Tumor Microenvironment Humans Head and neck cancer Immune Checkpoint Inhibitors 030304 developmental biology 0303 health sciences Squamous Cell Carcinoma of Head and Neck Cancer Correction Immunotherapy medicine.disease Immune checkpoint Oropharyngeal Neoplasms medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Tumour immunology Transcriptome CD8 |
| Zdroj: | British Journal of Cancer Br J Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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