Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies. •Chemokines CTACK and CXCL9 predict response to therapy in melanoma patients.•CD95 expression in CD8+ lymphocytes is a good prognostic marker for therapeutic response of melanoma patients.•PD-1 and CD161 are associated with a worse prognosis for melanoma patients submitted to neoadjuvant immunotherapy.•PD-L2+ B lymphocytes or myeloid cells is a poor prognostic marker for therapeutic response of melanoma patients.•Inhibitory markers in PBMC from non-responder melanoma patients are associated with an exhausted profile in the tumor.