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.