国际口腔医学杂志

国际口腔医学杂志 ›› 2024, Vol. 51 ›› Issue (1): 21-27.doi: 10.7518/gikq.2024021

• 口腔肿瘤学专栏 • 上一篇    下一篇

程序性死亡受体/配体免疫治疗策略在人乳头瘤病毒阳性头颈部鳞状细胞癌中的研究进展

刘世一(),陈中(),张素欣   

  1. 河北医科大学第四医院口腔科 石家庄 050011
  • 收稿日期:2023-05-15 修回日期:2023-09-12 出版日期:2024-01-01 发布日期:2024-01-10
  • 通讯作者: 陈中
  • 作者简介:刘世一，医师，硕士，Email：<email>LiuShiyi@stu.hebmu.edu.cn</email>
  • 基金资助:
    河北省卫生健康委员会老年病防治项目(13000022PO0860-410186E);河北省医学科学研究课题计划(20190695)

Progress in research into programmed death-1/programmed death-ligand 1 immunotherapy strategies in human papillomavirus-positive head and neck squamous cell carcinoma

Liu Shiyi(),Chen Zhong(),Zhang Suxin   

  1. Dept. of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Received:2023-05-15 Revised:2023-09-12 Online:2024-01-01 Published:2024-01-10
  • Contact: Zhong Chen
  • Supported by:
    Geriatric Disease Prevention and Control Project of Hebei Provincial Health Commission(13000022-PO0860410186E);Key Science and Technology Research Program of Hebei Province(20190695)

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摘要：

人乳头瘤病毒（HPV）感染已成为头颈部鳞状细胞癌（HNSCC）的主要致病因素之一，与HPV阴性相比，HPV阳性HNSCC表现出以程序性死亡受体（PD）为代表的多种免疫细胞及其效应分子的表达增加。PD-1/PD-L1高表达的患者与HPV阳性HNSCC患者存活率的显著提高相关。而HPV阳性HNSCC患者在接受抗PD-1/程序性死亡配体（PD-L1）免疫治疗后的客观缓解率、无进展生存期、总生存期等指标较HPV阴性HNSCC患者有所提高，提示HPV阳性HNSCC患者在接受抗PD-1/PD-L1免疫治疗上可能取得更好疗效。另外，PD-1/PD-L1抑制剂联合HPV癌症疫苗、双通路抑制剂等免疫治疗方案在HPV相关癌症中已发挥出独特的优势。根据HPV状态为患者制定个体化免疫治疗是一种有前景的治疗策略。

关键词: 头颈部鳞状细胞癌, 人乳头瘤病毒, 程序性死亡受体/配体, 免疫治疗

Abstract:

Human papillomavirus (HPV) infection has become one of the main pathogenic factors of head and neck squamous cell carcinoma (HNSCC). The expression levels of various immune cells and effector molecules, including programmed death (PD)-1 and programmed death-ligand 1, are higher in HPV-positive HNSCC samples than in HPV-negative samples. Furthermore, patients with HPV-positive HNSCC and high PD-1 or PD-L1 expression showed significantly improved survival. Moreover, patients with HPV-positive HNSCC and on anti-PD-1/PD-L1 immunotherapy showed hi-gher objective remission rate (ORR), progression-free survival (PFS), overall survival (OS) and other indicators than patients with HPV-negative HNSCCs, suggesting that the former received greater clinical benefits than the latter. In addition, HPV cancer vaccine combined with PD-1/PD-L1 inhibitors, dual pathway inhibitors and other immunotherapy regimens play distinct beneficial roles in HPV-related cancer. Therefore, tailoring immunotherapy to patients based on HPV status is a promising treatment strategy.

Key words: head and neck squamous cell carcinoma, human papillomavirus, programmed death-1/programmed death-ligand 1, immunotherapy

中图分类号: 

  • R782
1 Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma[J].Nat Rev Dis Primers, 2020, 6(1): 1-22.
2 Castellsagué X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3 680 patients[J]. J Natl Cancer Inst, 2016, 108(6): djv403.
3 Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice[J]. Nat Rev Immunol, 2020, 20(11): 651-668.
4 Kumar H. Progresses in immunotherapy[J]. Int Rev Immunol, 2020, 39(5): 203-204.
5 Gibson-Corley KN, Coppock J, Espinosa-Cotton M, et al. Clinical significance of activating interleu-kin 1 ligands in HPV-positive and HPV-negative HNSCCs[J]. FASEB J, 2020, 34(S1): 1.
6 Cochicho D, Esteves S, Rito M, et al. PIK3CA gene mutations in HNSCC: systematic review and correlations with HPV status and patient survival[J]. Cancers (Basel), 2022, 14(5): 1286.
7 von Witzleben A, Wang C, Laban S, et al. HNSCC: tumour antigens and their targeting by immunotherapy[J]. Cells, 2020, 9(9): 2103.
8 D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer[J]. N Engl J Med, 2007, 356(19): 1944-1956.
9 Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review[J]. Cancer Epidemiol Biomarkers Prev, 2005, 14(2): 467-475.
10 Hoppe-Seyler K, Bossler F, Braun JA, et al. The HPV E6/E7 oncogenes: key factors for viral carcinogenesis and therapeutic targets[J]. Trends Microbiol, 2018, 26(2): 158-168.
11 Rietbergen MM, Snijders PJ, Beekzada D, et al. Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas[J]. Int J Cancer, 2014, 134(10): 2366-2372.
12 Dok R, Glorieux M, Holacka K, et al. Dual role for p16 in the metastasis process of HPV positive head and neck cancers[J]. Mol Cancer, 2017, 16(1): 113.
13 Sewell A, Brown B, Biktasova A, et al. Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-associated head and neck cancer[J]. Clin Cancer Res, 2014, 20(9): 2300-2311.
14 Devaraja K, Aggarwal S, Verma SS, et al. Clinico-pathological peculiarities of human papilloma virus driven head and neck squamous cell carcinoma: a co-mprehensive update[J]. Life Sci, 2020, 245: 117383.
15 Zhang JL, Chen T, Yang XP, et al. Attenuated TRAF3 fosters activation of alternative NF-κB and reduced expression of antiviral interferon, TP53, and RB to promote HPV-positive head and neck cancers[J]. Cancer Res, 2018, 78(16): 4613-4626.
16 Faden DL, Ding F, Lin Y, et al. APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma[J]. Oral Oncol, 2019, 96: 140-147.
17 Combes JD, Dalstein V, Gheit T, et al. Prevalence of human papillomavirus in tonsil brushings and gargles in cancer-free patients: the SPLIT study[J]. Oral Oncol, 2017, 66: 52-57.
18 Li BN, Sui L. Metabolic reprogramming in cervical cancer and metabolomics perspectives[J]. Nutr Metab (Lond), 2021, 18(1): 93.
19 Kahue CN, Jerrell RJ, Parekh A. Expression of human papillomavirus oncoproteins E6 and E7 inhi-bits invadopodia activity but promotes cell migration in HPV-positive head and neck squamous cell carcinoma cells[J]. Cancer Rep (Hoboken), 2018, 1(3): e1125.
20 Wang BZ, Zhang SW, Tong FJ, et al. HPV+HNSCC-derived exosomal miR-9-5p inhibits TGF-β signa-ling-mediated fibroblast phenotypic transformation through NOX4[J]. Cancer Sci, 2022, 113(4): 1475-1487.
21 Lechner A, Schlößer HA, Thelen M, et al. Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma[J]. Oncoimmunology, 2019, 8(3): 1535293.
22 Chatfield-Reed K, Gui SY, O’Neill WQ, et al. HPV33+ HNSCC is associated with poor prognosis and has unique genomic and immunologic landscapes[J]. Oral Oncol, 2020, 100: 104488.
23 Hladíková K, Koucký V, Bouček J, et al. Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells[J]. J Immunother Cancer, 2019, 7(1): 261.
24 Ruffin AT, Cillo AR, Tabib T, et al. B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma[J]. Nat Commun, 2021, 12(1): 3349.
25 Forster MD, Devlin MJ. Immune checkpoint inhibition in head and neck cancer[J]. Front Oncol, 2018, 8: 310.
26 Lenouvel D, González-Moles MÁ, Ruiz-Ávila I, et al. Prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma: a systematic review and comprehensive meta-analysis[J]. Oral Oncol, 2020, 106: 104722.
27 Hwan KM, Jae-Hwan K, Min L, et al. Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune check-point blockade response[J]. Br J Cancer, 2020, 122(11): 1649-1660.
28 Wang J, Sun H, Zeng Q, et al. HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma[J]. Sci Rep, 2019, 9(1): 13404.
29 Cillo AR, Kürten CHL, Tabib T, et al. Immune landscape of viral- and carcinogen-driven head and neck cancer[J]. Immunity, 2020, 52(1): 183-199.e9.
30 Zagozdzon R, Winiarska M, Firczuk M. Immune evasion as the main challenge for immunotherapy of cancer[J]. Cancers (Basel), 2022, 14(15): 3622.
31 Li FG, Deng LG, Jackson KR, et al. Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations[J]. J Immunother Cancer, 2021, 9(7): e002531.
32 Sanchez-Canteli M, Hermida-Prado F, Sordo-Bahamonde C, et al. Lectin-like transcript 1 (LLT1) checkpoint: a novel independent prognostic factor in HPV-negative oropharyngeal squamous cell carcinoma[J]. Biomedicines, 2020, 8(12): 535.
33 Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuxi-mab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study[J]. Lancet, 2019, 394(10212): 1915-1928.
34 Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial[J]. Lancet Oncol, 2016, 17(7): 956-965.
35 Ferris RL, Blumenschein G, Fayette J, et al. Nivo-lumab for recurrent squamous-cell carcinoma of the head and neck[J]. N Engl J Med, 2016, 375(19): 1856-1867.
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