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, Sang Woo Kim, Sun Och Yoon, Yoon Woo Koh, Byoung Chul Cho, Hye Ryun Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalBritish journal of cancer
DOIs
Publication statusAccepted/In press - 2020 Jan 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kim, M. H., Kim, J. H., Lee, J. M., Choi, J. W., Jung, D., Cho, H., Kang, H., Hong, M. H., Heo, S. J., Kim, S. H., Choi, E. C., Kim, D. H., Park, Y. M., Kim, S. W., Yoon, S. O., Koh, Y. W., Cho, B. C., & Kim, H. R. (Accepted/In press). Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response. British journal of cancer. https://doi.org/10.1038/s41416-020-0796-8