British journal of cancer, 2020-05, Vol.122 (11), p.1649-1660
2020
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- Autor(en) / Beteiligte
- Titel
- Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response
- Ist Teil von
- British journal of cancer, 2020-05, Vol.122 (11), p.1649-1660
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. 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. 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). 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-0920eISSN: 1532-1827DOI: 10.1038/s41416-020-0796-8Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7251088
- Format
- –
- Schlagworte
- Apoptosis, CD73 antigen, CD8 antigen, Human papillomavirus, Humans, Immune checkpoint, Immune Checkpoint Inhibitors - therapeutic use, Immunohistochemistry, Immunotherapy, Lymphocytes T, Lymphocytes, Tumor-Infiltrating - immunology, Macrophages, Mesenchyme, Metastases, Microenvironments, Oropharyngeal cancer, Oropharyngeal Neoplasms - drug therapy, Oropharyngeal Neoplasms - genetics, Oropharyngeal Neoplasms - immunology, Patients, PD-1 protein, PD-L1 protein, Ribonucleic acid, RNA, Squamous Cell Carcinoma of Head and Neck - drug therapy, Squamous Cell Carcinoma of Head and Neck - genetics, Squamous Cell Carcinoma of Head and Neck - immunology, Throat cancer, Transcriptome, Tumor Microenvironment - immunology, Tumors