Prognostic values of immune efficacy biomarkers in the treatment of nasopharyngeal carcinoma

doi:10.3760/cma.j.cn371439-20201120-00147

Abstract

Abstract:

Immunotherapy has achieved objective response rates of 20%-30% in patients with recurrent or metastatic nasopharyngeal carcinoma, but fewer people are benefiting. Studies have shown that patients with nasopharyngeal carcinoma carrying high expression of programmed death-1/programmed death-ligand 1 and/or high tumor mutation burden have a significant response to immunotherapy. Biomarkers of the tumor microenvironment, especially tumor infiltrating lymphocyte, are abundant in nasopharyngeal carcinoma, varying from different Epstein-Barr virus states, which can also play a predictive role of immunotherapy efficacy. Other biomarkers, such as mismatch repair-deficient, have a low incidence in nasopharyngeal carcinoma and limited predictive power. Combined detection of different types of immunotherapeutic biomarkers is more helpful to identify suitable populations for immunotherapy.

Key words: Nasopharyngeal neoplasms, Immunotherapy, Biomarkers, tumor

Luo Wenxiao, Wu Dehua, Cai Longmei. Prognostic values of immune efficacy biomarkers in the treatment of nasopharyngeal carcinoma[J]. Journal of International Oncology, 2021, 48(12): 743-746.

References 32

[1]	Sun XS, Liu SL, Luo MJ, et al. The association between the deve-lopment of radiation therapy, image technology, and chemotherapy, and the survival of patients with nasopharyngeal carcinoma: a cohort study from 1990 to 2012[J]. Int J Radiat Oncol Biol Phys, 2019,105(3):581-590. DOI: 10.1016/j.ijrobp.2019.06.2549.
[2]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016,66(2):115-132. DOI: 10.3322/caac.21338.
[3]	Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial[J]. Lancet, 2016,388(10054):1883-1892. DOI: 10.1016/S0140-6736(16)31388-5.
[4]	Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab 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. DOI: 10.1016/S0140-6736(19)32591-7.
[5]	Hsu C, Lee SH, Ejadi S, et al. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1-positive nasopharyngeal carcinoma: results of the KEYNOTE-028 study[J]. J Clin Oncol, 2017,35(36):4050-4056. DOI: 10.1200/JCO.2017.73.3675.
[6]	Ribas A. Tumor immunotherapy directed at PD-1[J]. N Engl J Med, 2012,366(26):2517-2519. DOI: 10.1056/NEJMe1205943.
[7]	Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity[J]. Nature, 2017,545(7655):495-499. DOI: 10.1038/nature22396.
[8]	Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway[J]. N Engl J Med, 2016,375(18):1767-1778. DOI: 10.1056/NEJMra1514296.
[9]	Barone A, Hazarika M, Theoret MR, et al. FDA approval summary: pembrolizumab for the treatment of patients with unresectable or metastatic melanoma[J]. Clin Cancer Res, 2017,23(19):5661-5665. DOI: 10.1158/1078-0432.CCR-16-0664.
[10]	Pai-Scherf L, Blumenthal GM, Li H, et al. FDA approval sum-mary: pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond[J]. Oncologist, 2017,22(11):1392-1399. DOI: 10.1634/theoncologist.2017-0078.
[11]	Fashoyin-Aje L, Donoghue M, Chen H, et al. FDA approval summary: pembrolizumab for recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma expressing PD-L1[J]. Oncologist, 2019,24(1):103-109. DOI: 10.1634/theoncologist.2018-0221.
[12]	Chan OS, Kowanetz M, Ng WT, et al. Characterization of PD-L1 expression and immune cell infiltration in nasopharyngeal cancer[J]. Oral Oncol, 2017,67:52-60. DOI: 10.1016/j. oraloncology.2017.02.002.
[13]	Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the Mayo clinic phase 2 consortium (NCI-9742)[J]. J Clin Oncol, 2018,36(14):1412-1418. DOI: 10.1200/JCO.2017.77.0388.
[14]	Jiang F, Yu W, Zeng F, et al. PD-1 high expression predicts lower local disease control in stage Ⅳ M₀ nasopharyngeal carcinoma[J]. BMC Cancer, 2019,19(1):503. DOI: 10.1186/s12885-019-5689-y.
[15]	Huang ZL, Liu S, Wang GN, et al. The prognostic significance of PD-L1 and PD-1 expression in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis[J]. Cancer Cell Int, 2019,19:141. DOI: 10.1186/s12935-019-0863-5.
[16]	Lipson EJ, Velculescu VE, Pritchard TS, et al. Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade[J]. J Immunother Cancer, 2014,2(1):42. DOI: 10.1186/s40425-014-0042-0.
[17]	Wang HY, Li F, Liu N, et al. Prognostic implications of a molecular classifier derived from whole-exome sequencing in nasopharyngeal carcinoma[J]. Cancer Med, 2019,8(6):2705-2716. DOI: 10.1002/cam4.2146.
[18]	Ali SM, Yao M, Yao J, et al. Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy[J]. Cancer, 2017,123(18):3628-3637. DOI: 10.1002/cncr.30781.
[19]	Wang F, Wei XL, Wang FH, et al. Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ⅰb/Ⅱ clinical trial NCT02915432[J]. Ann Oncol, 2019,30(9):1479-1486. DOI: 10.1093/annonc/mdz197.
[20]	Gourzones C, Barjon C, Busson P. Host-tumor interactions in nasopharyngeal carcinomas[J]. Semin Cancer Biol, 2012,22(2):127-136. DOI: 10.1016/j.semcancer.2012.01.002.
[21]	Wang YQ, Chen YP, Zhang Y, et al. Prognostic significance of tumor-infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: a large-scale cohort study[J]. Int J Cancer, 2018,142(12):2558-2566. DOI: 10.1002/ijc.31279.
[22]	Zhu Q, Cai MY, Chen CL, et al. Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes[J]. Oncoimmunology, 2017,6(5):e1312240. DOI: 10.1080/2162402X.2017.1312240.
[23]	Lu J, Chen XM, Huang HR, et al. Detailed analysis of inflamma-tory cell infiltration and the prognostic impact on nasopharyngeal carcinoma[J]. Head Neck, 2018,40(6):1245-1253. DOI: 10.1002/hed.25104.
[24]	Ooft ML, van Ipenburg JA, Sanders ME, et al. Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma[J]. J Clin Pathol, 2018,71(3):267-274. DOI: 10.1136/jclinpath-2017-204664.
[25]	Chang CH, Qiu J, O'Sullivan D, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression[J]. Cell, 2015,162(6):1229-1241. DOI: 10.1016/j.cell.2015.08.016.
[26]	Ott PA, Bang YJ, Piha-Paul SA, et al. T-cell-inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028[J]. J Clin Oncol, 2019,37(4):318-327. DOI: 10.1200/JCO.2018.78.2276.
[27]	Zhang G, Xu Y, Zhou H. The infiltration of ICOS + cells in nasopharyngeal carcinoma is beneficial for improved prognosis [J]. Pathol Oncol Res, 2020,26(1):365-370. DOI: 10.1007/s12253-018-0509-2.
[28]	Lemery S, Keegan P, Pazdur R. First FDA approval agnostic of cancer site-when a biomarker defines the indication[J]. N Engl J Med, 2017,377(15):1409-1412. DOI: 10.1056/NEJMp1709968.
[29]	Chen FM, Zhang YX, Li XF, et al. The prognostic value of deficient mismatch repair in stage Ⅱ-Ⅳa nasopharyngeal carcinoma in the era of IMRT[J]. Sci Rep, 2020,10(1):9690. DOI: 10.1038/s41598-020-66678-3.
[30]	Zhao L, Liao X, Hong G, et al. Mismatch repair status and high expression of PD-L1 in nasopharyngeal carcinoma[J]. Cancer Manag Res, 2019,11:1631-1640. DOI: 10.2147/CMAR.S193878.
[31]	Ueda T, Chikuie N, Takumida M, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab[J]. Acta Otolaryngol, 2020,140(2):181-187. DOI: 10.1080/00016489.2019.1699250.
[32]	Ho WJ, Yarchoan M, Hopkins A, et al. Association between pretreatment lymphocyte count and response to PD1 inhibitors in head and neck squamous cell carcinomas[J]. J Immunother Cancer, 2018,6(1):84. DOI: 10.1186/s40425-018-0395-x.