PD-L1 and survival in oral cavity squamous cell carcinoma

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).

Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.

Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.

Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

1. Kaprin, A.D., Starinskyj, V.V., Petrova, G.V. (eds) Status of cancer care for the population of Russia in 2018 of the Russian Federation. Moscow: MNIOI n. P.A. Gercen; 2019. 236 p. (In Russ.). Available at: https://nnood.ru/wp-content/uploads/2019/04/Statichticheskijj-ezhegodnik-Gercena-2018.pdf.

2. Ferris R.L. Immunology and immunotherapy of head and neck cancer. J Clin Oncol. 2015;33(29):3293-304. https://doi:10.1200/JCO.2015.61.1509.

3. Ock C.Y., Keam B., Kim S., Lee J.S., Kim M., Kim T.M., Jeon Y.K., Kim D.W., Chung D.H., Heo D.S. Pan-cancer immunogenomic perspective on the tumor microenvironment based on PD-L1 and CD8 T cell. Clin Cancer Res. 2016;22(9):2261-2270. https://doi:10.1158/1078-0432.CCR-15-2834.

4. Taube J.M., Robert A.A., Young G.D., Xu H., Sharma R., McMiller T.L., Chen S., Klein A.P., Pardoll D.M., Topalian S.L., Chen L. Colocalization of inflammatory response with B7- h1 expression in human melanocytic lesions supportsan adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;127(4):127ra37. https://doi.org/10.1126/scitranslmed.3003689.

5. Partlova S., Bouček J., Kloudová K., Lukešová E., Zábrodský M., Grega M., Fučíková J., Truxová I., Tachezy R., Špíšek R., Fialová A. Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma. Oncoimmunology. 2015;4(1):e965570. https://doi.org/10.4161/21624011.2014.965570.

6. D’Incecco A., Andreozzi M., Ludovini V., Rossi E., Capodanno A., Landi L., Tibaldi C., Minuti G., Salvini J., Coppi E., Chella A., Fontanini G., Filice M.E., Tornillo L., Incensati R.M., Sani S., Crinò L., Terracciano L., Cappuzzo F. PD-1 and PDL1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102. https://doi.org/10.1038/bjc.2014.555.

7. Vassilakopoulou M., Avgeris M., Velcheti V., Kotoula V., Rampias T., Chatzopoulos K., Perisanidis C., Kontos C.K., Giotakis A.I., Scorilas A., Rimm D., Sasaki C., Fountzilas G., Psyrri A. Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma. Clin Cancer Res. 2016;22(3):704-713. https://doi.org/10.1158/1078-0432.ccr-15-1543.

8. Kutukova, S.I., Belyak, N.P., Raskin, G.A., Mukhina, M.S., Kuzminova, M.V., Pestova, N.E., Manikhas, G.M., Yaremenko, A.I., Ivaskova. Yu.V. The prognostic value of PDL1 expression in tumor and immune cells in squamous cell carcinoma of the oral mucosa. Problems in Oncology. 2017;63(5):759-765. Available at: https://www.elibrary.ru/item.asp?id=30779777.

9. Hanna G.J., Woo S.-B., Li Y.Y., Barletta J.A., Hammerman P.S., Lorch J.H. Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018;47(5):568-577. https://doi.org/10.1016/j.ijom.2017.09.006.

10. Vicente J.C., Rodríguez-Santamarta T., Rodrigo J. P., Blanco-Lorenzo V., Allonca E., García-Pedrero J.M. PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma. Cancer Epidemoil Biomarkers Prev. 2019;Mar;28(3):546-554. https://doi.org/10.1158/1055-9965.EPI-18-0779.

11. Yoshida S., Nagatsuka H., Nakano K., Kogashiwa Y., Ebihara Y., Yano M., Yasuda M. Significance of PDL1 Expression in Tongue Cancer Development. Int J Med Sci. 2018;15(14):1723-1730. https://doi.org/10.7150/ijms.27860.