The relationships between PD-L1 expression,CD8+ TILs and clinico-histomorphological parameters in malignant melanomas |
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| Institution: | 1. Alphamedical s.r.o., Záborského 2, 038 61, Martin, Slovakia;2. Hermes LabSystems, s.r.o., Púchovská 12, 83106, Bratislava, Slovakia;3. Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Anatomy, Malá Hora 4, 036 01, Martin, Slovakia;4. Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Histology and Embryology, Malá Hora 4, 036 01, Martin, Slovakia;1. Department of Anesthesiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China;2. Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China;1. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, PR China;2. Department of Environmental Occupational Health, Taizhou Center for Disease Control and Prevention, No.318 Yongtai Road, Hailing District, Taizhou City, Jiangsu Province, PR China;1. Unit of Pathology, Dept. of Medicine and Surgery, University of Insubria, Varese, Italy;2. Unit of Internal Medicine, Dept. of Medicine and Surgery, University of Insubria, Varese, Italy;3. Dept. of Oncology, ASST Sette Laghi, Varese, Italy;4. Dept. of Medical, Oral and Biotechnology Sciences, University of Chieti, Italy;5. Dept. of Pathology, ASST Sette Laghi, Varese, Italy;1. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran;2. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, United States;3. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran;4. Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran;5. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran;6. Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran;7. Paul G. Allen Center for Computer Science &Engineering, University of Washington, United States;8. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;9. Student Research Committee, Kashan University of Medical Sciences, Kashan, I.R., Iran;10. Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan;11. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;12. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran |
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| Abstract: | IntroductionMalignant melanomas (MM) are often connected with the expression of PD-L1 protein and the presence of tumor-infiltrating lymphocytes (TILs), however, their impact on prognosis remains controversial. Due to their supposed clinical significance and lack of convincing data, we decided to establish the relationships between CD8 + TIL count, PD-L1 level and certain clinical and histopathological parameters in patients with malignant melanoma, especially those associated with unfavorable prognosis.Materials and methodsWe performed immunohistochemistry for PD-L1 and CD8 on 56 formalin-fixed paraffin-embedded specimens from patients with cutaneous and metastatic malignant melanomas. PD-L1 expression levels were determined by immunohistochemistry (clone 28-8) and subsequently the tumor proportion scores (TPS) were evaluated. CD8 + TIL expressions were classified as either grade 0, 1+, 2+ or 3+, based on the density and distribution of the infiltrating lymphocytes.ResultsThe PD-L1 expression was detected in 20 out of 56 cases (35,71 %). The expression of PD-L1 on tumor cells was significantly increased with higher TILs infiltration in the tumor microenvironment (p = 0,038). Lower TIL score corresponds with poor prognostic clinicopathological parameters such as higher number of mitotic figures (p = 0,005), Clark's level (p = 0,007) and Breslow's depth (p = 0,010).ConclusionsOur results suggest a favorable prognostic value for CD8 + TIL infiltration. Moreover, TIL density was strongly correlated and geographically associated to PD-L1 expression. This analysis provides more insight into the role of TIL count and PD-L1 level in MM and their relationship with each other and association with other prognostic indicators. |
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| Keywords: | Malignant melanoma Protein PD-L1 Tumor infiltrating lymphocytes |
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