Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
09
09
2019
accepted:
24
02
2020
revised:
11
02
2020
pubmed:
3
4
2020
medline:
20
3
2021
entrez:
3
4
2020
Statut:
ppublish
Résumé
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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 32235905
doi: 10.1038/s41416-020-0796-8
pii: 10.1038/s41416-020-0796-8
pmc: PMC7251088
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1649-1660Subventions
Organisme : Daewoong Pharmaceutical Company (Daewoong)
ID : DF-201906-0000001
Organisme : Yonsei University | Yonsei University College of Medicine (YUCM)
ID : No. 6-2017-0104
Organisme : National Research Foundation of Korea (NRF)
ID : 2017M3A9E802971, 2017M3A9E9072669
Organisme : Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)
ID : HA16C0015020019
Commentaires et corrections
Type : ErratumIn
Références
Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541–550 (2018).
doi: 10.1038/s41591-018-0014-x
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y. et al. TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544–548 (2018).
doi: 10.1038/nature25501
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015).
doi: 10.1126/science.aaa1348
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V. et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 359, 582–587 (2018).
doi: 10.1126/science.aao4572
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).
doi: 10.1126/science.aan4236
Pulte, D. & Brenner, H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist 15, 994–1001 (2010).
doi: 10.1634/theoncologist.2009-0289
Ferris, R. L., Blumenschein, G. Jr., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L. et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 375, 1856–1867 (2016).
doi: 10.1056/NEJMoa1602252
Bauml, J., Seiwert, T. Y., Pfister, D. G., Worden, F., Liu, S. V., Gilbert, J. et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J. Clin. Oncol. 35, 1542–1549 (2017).
doi: 10.1200/JCO.2016.70.1524
Tourneau C. L., Cohen, E. E. W., Harrington, K. J., Dinis, J., Licitra, L., Ahn, M. et al. Pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): post hoc analyses of treatment options from the Phase III KEYNOTE-040 Trial. Ann. Oncol. 29 (Suppl_8), viii372–viii399 (2018).
Ang, K. K., Harris, J., Wheeler, R., Weber, R., Rosenthal, D. I., Nguyen-Tan, P. F. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N. Engl. J. Med. 363, 24–35 (2010).
doi: 10.1056/NEJMoa0912217
Leemans, C. R., Braakhuis, B. J. & Brakenhoff, R. H. The molecular biology of head and neck cancer. Nat. Rev. Cancer 11, 9–22 (2011).
doi: 10.1038/nrc2982
Mandal, R., Senbabaoglu, Y., Desrichard, A., Havel, J. J., Dalin, M. G., Riaz, N. et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 1, e89829 (2016).
doi: 10.1172/jci.insight.89829
Zhang, Y., Koneva, L. A., Virani, S., Arthur, A. E., Virani, A., Hall, P. B. et al. Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number alterations, PIK3CA mutation, and pathway signatures. Clin. Cancer Res. 22, 4735–4745 (2016).
doi: 10.1158/1078-0432.CCR-16-0323
Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576–582 (2015).
Chung, C. H., Parker, J. S., Karaca, G., Wu, J., Funkhouser, W. K., Moore, D. et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 5, 489–500 (2004).
doi: 10.1016/S1535-6108(04)00112-6
Lim, S. M., Cho, S. H., Hwang, I. G., Choi, J. W., Chang, H., Ahn, M. J. et al. Investigating the feasibility of targeted next-generation sequencing to guide the treatment of head and neck squamous cell carcinoma. Cancer Res. Treat. https://doi.org/10.4143/crt.2018.012 (2018).
Hanzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinform. 14, 7 (2013).
doi: 10.1186/1471-2105-14-7
Zheng, C., Zheng, L., Yoo, J. K., Guo, H., Zhang, Y., Guo, X. et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169, 1342–1356 (2017). e1316.
doi: 10.1016/j.cell.2017.05.035
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H. 2nd, Treacy, D., Trombetta, J. J. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
doi: 10.1126/science.aad0501
Newman, A. M., Liu, C. L., Green, M. R., Gentles, A. J., Feng, W., Xu, Y. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453–457 (2015).
doi: 10.1038/nmeth.3337
Jiang, P., Gu, S., Pan, D., Fu, J., Sahu, A., Hu, X. et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat. Med. 24, 1550–1558 (2018).
doi: 10.1038/s41591-018-0136-1
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S. et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 165, 35–44 (2016).
doi: 10.1016/j.cell.2016.02.065
Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J. et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 362 (2018). pii: eaar3593. https://doi.org/10.1126/science.aar3593 .
Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A., Behjati, S., Biankin, A. V. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
doi: 10.1038/nature12477
Wang, S., Jia, M., He, Z. & Liu, X. S. APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer. Oncogene 37, 3924–3936 (2018).
doi: 10.1038/s41388-018-0245-9
de Ruiter, E. J., Ooft, M. L., Devriese, L. A. & Willems, S. M. The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. Oncoimmunology 6, e1356148 (2017).
doi: 10.1080/2162402X.2017.1356148
Mahmoud, S. M., Paish, E. C., Powe, D. G., Macmillan, R. D., Grainge, M. J., Lee, A. H. et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J. Clin. Oncol. 29, 1949–1955 (2011).
doi: 10.1200/JCO.2010.30.5037
Schalper, K. A., Brown, J., Carvajal-Hausdorf, D., McLaughlin, J., Velcheti, V., Syrigos, K. N. et al. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J. Natl Cancer Inst. 107 (2015). pii: dju435. https://doi.org/10.1093/jnci/dju435 .
Lyford-Pike, S., Peng, S., Young, G. D., Taube, J. M., Westra, W. H., Akpeng, B. et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 73, 1733–1741 (2013).
doi: 10.1158/0008-5472.CAN-12-2384
Albers, A., Abe, K., Hunt, J., Wang, J., Lopez-Albaitero, A., Schaefer, C. et al. Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Cancer Res. 65, 11146–11155 (2005).
doi: 10.1158/0008-5472.CAN-05-0772
Nasman, A., Romanitan, M., Nordfors, C., Grun, N., Johansson, H., Hammarstedt, L. et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS ONE 7, e38711 (2012).
doi: 10.1371/journal.pone.0038711
Krishna, S., Ulrich, P., Wilson, E., Parikh, F., Narang, P., Yang, S. et al. Human papilloma virus specific immunogenicity and dysfunction of CD8(+) T cells in head and neck cancer. Cancer Res. 78, 6159–6170 (2018).
doi: 10.1158/0008-5472.CAN-18-0163
Bailey, M. H., Tokheim, C., Porta-Pardo, E., Sengupta, S., Bertrand, D., Weerasinghe, A. et al. Comprehensive characterization of cancer driver genes and mutations. Cell 173, 371–385 (2018). e318.
doi: 10.1016/j.cell.2018.02.060