Clinical significance of PD-L1 and tumor immune microenvironment in predicting neoadjuvant therapy for oral squamous cell carcinoma

doi:10.19438/j.cjoms.2023.06.007

Abstract

Abstract: PURPOSE: To explore the clinical significance of the expression of programmed cell death-ligand 1(PD-L1) and tumor immune microenvironment for the evaluation of the efficacy of neoadjuvant immunotherapy combined with chemotherapy in oral squamous cell carcinoma(OSCC). METHODS: The clinical data of 20 patients with OSCC who received neoadjuvant therapy in the Department of Oral Surgery of the First Medical Center of PLA General Hospital from August to December 2019 were retrospectively analyzed. The expression of PD-L1 in OSCC was detected by immunohistochemical staining. The expression levels of CD8⁺ T lymphocytes, CD68⁺ macrophages, PD-1⁺ cells, CD8⁺PD-1⁺ T lymphocytes and CD68⁺PD-L1⁺ macrophages in the immune microenvironment of OSCC were detected by multiple fluorescent immunohistochemical staining (mIHC). SPSS 21.0 software package was used for data analysis. RESULTS: The positive expression rates of PD-L1 in OSCC were 65% and 85% under the criteria of tumor proportion score(TPS)≥1% and combined positive score(CPS)≥1, respectively, and the high expression of PD-L1 (CPS≥20) accounted for 50%. There was no significant correlation between PD-L1 expression and age, sex, tumor differentiation and cervical lymph node metastasis (P>0.05). The clinical response rate after 2 cycles of neoadjuvant therapy was 55%. Survival analysis showed that the progression-free survival(PFS) and disease-free survival(DFS) of PD-L1 positive expression group were significantly higher than those of PD-L1 negative expression group (P<0.05). The expression of PD-L1 in OSCC was positively correlated with CD68⁺PD-L1⁺macrophages accounting for more than 50%, and the clinical response rate of patients with positive expression of PD-L1 and CD68⁺PD-L1⁺ macrophages accounting for more than 50% was 70% after neoadjuvant therapy. CONCLUSIONS: Neoadjuvant immunotherapy combined with chemotherapy may further prolong the DFS of patients with OSCC with positive expression of PD-L1. The high expression of CD68⁺PD-L1⁺ macrophage has important clinical significance for evaluating the efficacy of neoadjuvant therapy for OSCC.

Key words: Oral squamous cell carcinoma, OSCC, Neoadjuvant Immunotherapy, Chemotherapy, PD-1/PD-L1, Tumor immune microenvironment

CLC Number:

R739.8

JIN Neng-hao, TIAN Yu, ZHU Liang, QIAO Bo, LI Liang-bo, ZHANG Hai-zhong, ZHANG Lei. Clinical significance of PD-L1 and tumor immune microenvironment in predicting neoadjuvant therapy for oral squamous cell carcinoma[J]. China Journal of Oral and Maxillofacial Surgery, 2023, 21(6): 572-578.

References

[1] Bray F, Ferlay J, Soerjomataram I, et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2] Siegel RL, Ward E, Brawley O, et al.Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[J]. CA Cancer J Clin, 2011, 61(4): 212-236.
[3] Gyawali B, Shimokata T, Honda K, et al.Chemotherapy in locally advanced head and neck squamous cell carcinoma[J]. Cancer Treat Rev, 2016, 44: 10-16.
[4] Sadreddini S, Baradaran B, Aghebati-Maleki A, et al.Immune checkpoint blockade opens a new way to cancer immunotherapy[J]. J Cell Physiol, 2019, 234(6): 8541-8549.
[5] Larkin J, Hodi FS, Wolchok JD, et al.Combined nivolumab and Ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med, 2015, 373(1): 1270-1271.
[6] Reck M, Rodriguez-Abreu D, Robinson AG, et al.Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J]. N Engl J Med, 2016, 375(19): 1823-1833.
[7] 雷静, 赵周社, 史大鹏, 等. 实体瘤影像学疗效评价标准及其评估进展[J]. 功能与分子医学影像学(电子版), 2015, 4(1): 619-625.
Lei J, Zhao ZS, Shi DP, et al.Progress of image evaluation criteria in solid tumors[J]. Functional and Molecular Medical Imaging(Electronic Edition), 2015, 4(1): 619-625.
[8] Maloney A, Clarke PA, Naabyhansen S, et al.Gene and protein expression profiling of human ovarian cancer cells treated with the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin[J]. Cancer Res, 2007, 67(7): 3239-3253.
[9] Zou W, Wolchok JD, Chen L.PD-L1(B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations[J]. Sci Transl Med, 2016, 8(328): 324-328.
[10] Chen K, Huang HT, Hang WJ, et al.Effects of lung cancer cellassociated B7-H1 on T-cell proliferation in vitro and in vivo[J]. Braz J Med Biol Res, 2016, 49(7): e5263.
[11] Michalek RD, Gerriets VA, Jacobs SR, et al.Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets[J]. J Immunol, 2011, 186(6): 3299-3303.
[12] 宋楠, 李涛, 张学敏, 等. 免疫细胞与肿瘤微环境[J]. 生物化学与生物物理进展, 2014, 41(10): 1075-1084.
Song N, Li T, Zhang XM, et al.Immune cells in tumor microenvironment[J]. Progress in Biochemistry & Biophysics, 2014, 41(10): 1075-1084.
[13] Wang X, Teng F, Kong L, et al.PD-L1 expression in human cancers and its association with clinical outcomes[J]. Onco Targets Ther, 2016, 9: 5023-5039.
[14] Baci D, Bosi A, Gallazzi M, et al. The ovarian cancer tumor immune microenvironment (TIME) as target for therapy: a focus on innate immunity cells as therapeutic effectors[J]. Int J Mol Sci, 2020, 21(9)∶ 3125.
[15] Sasada T, Suekane S.Variation of tumor-infiltrating lymphocytes in human cancers: controversy on clinical significance[J]. Immunotherapy, 2011, 3(10): 1235-1251.
[16] Xu Q, Wang C, Yuan X, et al.Prognostic value of tumor-infiltrating lymphocytes for patients with head and neck squamous cell carcinoma[J]. Transl Oncol, 2017, 10(1): 10-16.
[17] Shimizu S, Hiratsuka H, Koike K, et al.Tumor-infiltrating CD8+ T-cell density is an independent prognostic marker for oral squamous cell carcinoma[J]. Cancer Med, 2019, 8(1): 80-93.
[18] Clarke JM,George DJ, Lisi S, et al.Immune checkpoint blockade: the new frontier in cancer treatment[J]. Target Oncol, 2018, 13(1): 1-20.
[19] Cohen EEW, Bell RB, Bifulco CB, et al.The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)[J]. J Immunother Cancer, 2019, 7(1): 184-214.
[20] Stafford M, Kaczmar J.The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC[J]. Cancers Head Neck, 2020, 5: 4-12.
[21] Uppaluri R, Campbell KM, Egloff AM, et al.Neoadjuvant and adjuvant pembrolizumab in resectable locally advanced, human papillomavirus-unrelated head and neck cancer: a multicenter, phase Ⅱ trial[J]. Clin Cancer Res, 2020, 26(19): 5140-5152.
[22] Lu Z, Wang J, Shu Y, et al.Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial[J]. BMJ, 2022, 377: e068714.
[23] Emens LA, Middleton G.The interplay of immunotherapy and chemotherapy: harnessing potential synergies[J]. Cancer Immunol Res, 2015, 3(5): 436-443.