Inhibitors of the PD-1/PD-L1 axis for the treatment of head and neck cancer: Current status and future perspectives
Open accessAbstract
Abstract: Head and neck cancer (HNC) is a common malignant tumor, but traditional therapeutic methods have unsatisfactory curative effects and many complications occur. Hence, there is an urgent need to develop therapeutic methods that can elicit curative effects as well as low toxic and few side effects. With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for HNC treatment. Groundbreaking progress has been achieved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). This review describes current treatment by PD-1- and PD-L1-targeted drugs for HNC. Keywords: head and neck cancer, squamous cell carcinoma, programmed cell death 1, programmed cell death ligand 1, immunotherapy, immune checkpoint
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Expression of PD-L1 was found to be increased by inflammatory factors, particularly interferon-γ, in the tumour microenvironment.
“Expression of PD-L1 was found to be increased by inflammatory factors particularly, interferon-γ in TME [101].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [101]
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Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015) · International Journal of Cancer · doi:10.1002/ijc.29210 · Cited by 28,766 · see citing works
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709 · see citing works
Cancer treatment and survivorship statistics, 2016
Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., Stein, K. D., Alteri, R., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21349 · Cited by 6,066 · see citing works
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck
Ferris, R. L., Blumenschein, G., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L., Harrington, K., Kasper, S., Vokes, E. E., Even, C., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1602252 · Cited by 5,101 · see citing works
Cancer treatment and survivorship statistics, 2022
Miller, K. D., Nogueira, L., Devasia, T. P., Mariotto, A. B., Yabroff, K. R., Jemal, A., Kramer, J. L., & Siegel, R. L. (2022) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21731 · Cited by 3,690 · see citing works
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012
Stimpfel, M., & Virant‐Klun, I. (2016) · Journal of Cancer Stem Cell Research · doi:10.14343/jcscr.2016.4e1003 · Cited by 2,723 · see citing works
Noman, M. Z., Desantis, G., Janji, B., Hasmim, M., Karray, S., Dessen, P., Bronte, V., & Chouaib, S. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131916 · Cited by 2,166 · see citing works
Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Deng, L., Liang, H. L., Burnette, B., Beckett, M., Darga, T. E., Weichselbaum, R. R., & Fu, Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67313 · Cited by 2,101 · see citing works
Seiwert, T. Y., Burtness, B., Mehra, R., Weiss, J., Berger, R., Eder, J. P., Heath, K., McClanahan, T., Lunceford, J., Gause, C., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30066-3 · Cited by 1,745 · cited 2× · see citing works
“Seiwert et al 16 used pembrolizumab to treat 60 patients with recurrent/metastatic HNSCC.”
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway
Boussiotis, V. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1514296 · Cited by 1,342 · see citing works
Green, M. R., Monti, S., Rodig, S. J., Juszczyński, P., Currie, T., O'Donnell, E., Chapuy, B., Takeyama, K., Neuberg, D. S., Golub, T. R., et al. (2010) · Blood · doi:10.1182/blood-2010-05-282780 · Cited by 1,307 · see citing works
Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A. B., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0310 · Cited by 1,237 · see citing works
Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma
Gillison, M. L., Chaturvedi, A. K., Anderson, W. F., & Fakhry, C. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.61.6995 · Cited by 1,223 · see citing works
Chow, L. Q. M., Haddad, R. I., Gupta, S., Mahipal, A., Mehra, R., Tahara, M., Berger, R., Eder, J. P., Burtness, B. A., Lee, S., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.68.1478 · Cited by 859 · see citing works
Lyford-Pike, S., Peng, S., Young, G. D., Taube, J. M., Westra, W. H., Akpeng, B., Bruno, T. C., Richmon, J. D., Wang, H., Bishop, J. A., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2384 · Cited by 777 · see citing works
Regulation of PD-L1: a novel role of pro-survival signalling in cancer.
Chen, J., Jiang, C. C., Jin, L., & Zhang, X. D. (2016) · Annals of Oncology · doi:10.1093/annonc/mdv615 · Cited by 767 · see citing works
Marzec, M., Zhang, Q., Goradia, A., Raghunath, P. N., Liu, X., Paessler, M. E., Wang, H. Y., Wysocka, M., Cheng, M. M., Ruggeri, B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810958105 · Cited by 731 · see citing works
Cancers with increasing incidence trends in the United States: 1999 through 2008
Simard, E. P., Ward, E., Siegel, R. L., & Jemal, A. (2012) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20141 · Cited by 723 · see citing works
Grégoire, V., Lefebvre, J. L., Licitra, L. F., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq185 · Cited by 629 · see citing works
American Cancer Society Head and Neck Cancer Survivorship Care Guideline
Cohen, E. E. W., LaMonte, S. J., Erb, N. L., Beckman, K. L., Sadeghi, N., Hutcheson, K. A., Stubblefield, M. D., Abbott, D. M., Fisher, P., Stein, K., et al. (2016) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21343 · Cited by 620 · see citing works
Antonia, S., Goldberg, S. B., Balmanoukian, A., Chaft, J. E., Sanborn, R. E., Gupta, A., Narwal, R., Steele, K., Gu, Y., Karakunnel, J. J., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00544-6 · Cited by 602 · see citing works
Oral complications of cancer and cancer therapy
Epstein, J. B., Thariat, J., Bensadoun, R., Barasch, A., Murphy, B. A., Kolnick, L., Popplewell, L. L., & Maghami, E. G. (2012) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21157 · Cited by 523 · see citing works
Structural and Functional Analysis of the Costimulatory Receptor Programmed Death-1
Zhang, X., Schwartz, J.-C. D., Guo, X., Bhatia, S., Cao, E., Chen, L., Zhang, Z., Edidin, M. A., Nathenson, S. G., & Almo, S. C. (2004) · Immunity · doi:10.1016/s1074-7613(04)00051-2 · Cited by 411 · see citing works
Fang, W., Zhang, J., Hong, S., Zhan, J., Chen, N., Qin, T., Tang, Y., Zhang, Y., Kang, S., Zhou, T., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2608 · Cited by 398 · see citing works
Structure and Interactions of the Human Programmed Cell Death 1 Receptor
Cheng, X., Veverka, V., Radhakrishnan, A., Waters, L. C., Muskett, F. W., Morgan, S. H., Huo, J., Yu, C., Evans, E. J., Leslie, A. J., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.448126 · Cited by 325 · see citing works
Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers
Derks, S., Liao, X., Chiaravalli, A. M., Xu, X., Camargo, M. C., Solcia, E., Sessa, F., Fleitas, T., Freeman, G. J., Rodig, S. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9076 · Cited by 308 · see citing works
Concha‐Benavente, F., Srivastava, R. M., Trivedi, S., Lei, Y. L., Chandran, U. R., Seethala, R. R., Freeman, G. J., & Ferris, R. L. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-2001 · Cited by 306 · see citing works
Westra, W. H. (2009) · Head and Neck Pathology · doi:10.1007/s12105-009-0100-y · Cited by 275 · see citing works
The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas
Benson, E. M., Li, R., Eisele, D. W., et al. (2013) · Oral Oncology · doi:10.1016/j.oraloncology.2013.09.008 · Cited by 251 · see citing works
Ahmed, K. A., Stallworth, D. G., Kim, Y., Johnstone, P. A. S., Harrison, L. B., Caudell, J. J., Yu, H., Etame, A. B., Weber, J. S., & Gibney, G. T. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv622 · Cited by 239 · see citing works
Lee, Y., Shin, J. H., Longmire, M. R., Wang, H., Kohrt, H. E. K., Chang, H. Y., & Sunwoo, J. B. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2665 · Cited by 221 · see citing works
Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma
Cohen, R. B., Delord, J., Doi, T., Piha-Paul, S. A., Liu, S. V., Gilbert, J., Algazi, A. P., Damian, S., Hong, R., Tourneau, C. L., et al. (2018) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000429 · Cited by 206 · see citing works
Akbari, O., Stock, P., Singh, A. K., Lombardi, V., Lee, W.-L., Freeman, G. J., Sharpe, A. H., Umetsu, D. T., & DeKruyff, R. H. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.112 · Cited by 182 · see citing works
Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody.
Segal, N. H., Antonia, S. J., Brahmer, J. R., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.3002 · Cited by 173 · see citing works
Straub, M., Drecoll, E., Pfarr, N., Weichert, W., Langer, R., Hapfelmeier, A., Götz, C., Wolff, K., Kolk, A., & Specht, K. (2016) · Oncotarget · doi:10.18632/oncotarget.7593 · Cited by 162 · see citing works
Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma
Liniker, E., Menzies, A. M., Kong, B. Y., Cooper, A. J., Ramanujam, S., Lo, S., Kefford, R. F., Fogarty, G. B., Guminski, A. D., Wang, W., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1214788 · Cited by 152 · see citing works
B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism
Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.4.2530 · Cited by 141 · see citing works
Yu, G., Bu, L., Huang, C., Zhang, W., Chen, W.-J., Gutkind, J. S., Kulkarni, A. B., & Sun, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.5955 · Cited by 101 · see citing works
Jie, H.-B., Srivastava, R. M., Argiris, A. E., Bauman, J. E., Kane, L., & Ferris, R. L. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0333 · Cited by 101 · see citing works
PD-L1 Blockade for Cancer Treatment: MEDI4736
Ibrahim, R. A., Stewart, R. A., & Shalabi, A. M. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.02.007 · Cited by 94 · see citing works
Kanda, S., Goto, K., Shiraishi, H., Kubo, E., Tanaka, A., Utsumi, H., Sunami, K., Kitazono, S., Mizugaki, H., Horinouchi, H., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw416 · Cited by 94 · see citing works
Promising New Molecular Targeted Therapies in Head and Neck Cancer
Dorsey, K., & Agulnik, M. (2013) · Drugs · doi:10.1007/s40265-013-0025-3 · Cited by 89 · see citing works
Segal, N. H., Ou, S. I., Balmanoukian, A. S., Fury, M. G., Massarelli, E., Brahmer, J. R., Weiss, J., Schöffski, P., Antonia, S. J., Massard, C., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.3011 · Cited by 80 · see citing works
The role of antagonists of the PD-1:PD-L1/PD-L2 axis in head and neck cancer treatment
Pai, S. I., Zandberg, D. P., & Strome, S. E. (2016) · Oral Oncology · doi:10.1016/j.oraloncology.2016.08.001 · Cited by 68 · see citing works
Human Papillomavirus–Negative Pharyngeal Cancer
Dillon, M. T., & Harrington, K. J. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.7804 · Cited by 53 · see citing works
Moreno, B. H., Parisi, G., Robert, L., & Ribas, A. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.02.008 · Cited by 49 · see citing works
Structural and Functional Analysis of the Costimulatory Receptor Programmed Death-1
Zhang, X., Schwartz, J.-C. D., Guo, X., Bhatia, S., Cao, E., Lorenz, M. C., Cammer, M., Chen, L., Zhang, Z., Edidin, M. A., et al. (2004) · Immunity · doi:10.1016/s1074-7613(04)00114-1 · Cited by 46 · see citing works
Fury, M. G., Ou, S. I., Balmanoukian, A. S., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu340.3 · Cited by 31 · see citing works
Bauml, J. M., Seiwert, T. Y., Pfister, D. G., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.6011 · Cited by 22 · see citing works
Adaptive immune resistance in HPV-associated head and neck squamous cell carcinoma
Pai, S. I. (2013) · OncoImmunology · doi:10.4161/onci.24065 · Cited by 17 · see citing works
Straub, M., Drecoll, E., Pfarr, N., et al. (2016) · doi:10.7892/boris.92049 · Cited by 16 · see citing works
Cohen, R. B., Delord, J., Doi, T., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.6017 · Cited by 12 · see citing works
Yao, Q., Fischer, K. P., Tyrrell, D. L., et al. (2014) · International Journal of Immunogenetics · doi:10.1111/iji.12175 · Cited by 8 · see citing works
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Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
Ford, K., Hanley, C. J., Mellone, M., Szyndralewiez, C., Heitz, F., Wiesel, P., Wood, O., Machado, M., Lopez, M.-A., Ganesan, A.-P., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3158 · Cited by 411 · see citing works
- Authors
- Ran, X., & Yang, K.
- Affiliations
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Yang, Kai
- ORCID
- Yang, Kai
- Venue
- Drug Design Development and Therapy
- Publisher
- Informa UK Limited
- Published
- 2017-07
- Volume
- Volume 11
- Pages
- 2007-2014
- ISSN
- 1177-8881 (ISSN-L)
- PMC
- PMC5501623
- OpenAlex
- W2726184669
- Cited by
- 51
- References
- 53
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 2 · 2013: 1
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Design Development and Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- head and neck cancer, head and neck squamous cell carcinoma, PD-1, PD-L1, immune checkpoint inhibitors, immunotherapy, targeted therapy, recurrent or metastatic cancer
- MeSH terms
- Animals, Antibodies, Monoclonal, Antineoplastic Agents, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Humans, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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