Tumor-infiltrating immune cell types predicting recurrence-free survival in melanoma patients receiving adjuvant PD-1 inhibitor therapy

Background Adjuvant treatment of melanoma patients with PD-1-based immunotherapy has improved recurrence rate, and became a standard treatment. However, a considerable proportion of patients recur within 1–2 years, necessitating the identification of predictive markers. Our study aimed to examine the association of intratumoral infiltration by specific immune cell subsets with the recurrence-free survival of melanoma patients receiving adjuvant PD-1 inhibitor therapy. Materials and methods Archived paraffin blocks of pretreatment surgical samples from 48 melanoma patients receiving adjuvant PD-1 inhibitor therapy were selected. Intratumoral density of immune cells expressing the following markers: CD8, FOXP3, CD20, CD103, CD134, PD-1, and PD-L1 was determined by immunohistochemistry, and the associations with recurrence-free survival were analyzed. Results Eighteen of the 48 patients developed recurrence during the follow-up period. In this group the ratio of patients showing strong immune cell infiltration (higher than the cutoff values defined by ROC curve analysis) was significantly lower compared to recurrence-free patients in the case of CD8 + T cells (2/18 vs. 16/30, p=0.0050), CD103 + tissue resident T cells (2/18 vs. 13/30, p=0.0259), and the activation/immune checkpoint markers CD134 (4/17 vs. 21/30, p=0.0029) and PD-1 (2/18 vs. 14/30, p=0.0134), while the evaluation of FOXP3 + cells yielded near significant trend (8/18 vs. 22/30, p=0.0663). High intratumoral density of the above cell types was accompanied with significantly longer recurrence-free survival. Conclusions Our findings indicate the importance of immune cell infiltration in the efficacy of adjuvant PD-1 inhibitor treatment in a “real world” patient cohort.