The relationships between PD-L1 expression, CD8+ TILs and clinico-histomorphological parameters in malignant melanomas.

INTRODUCTION

Malignant 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 METHODS

We 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.

RESULTS

The 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).

CONCLUSIONS

Our 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.