CD38hiCD19dim cells in lymph nodes predict favorable prognosis in patients with stage III melanoma receiving adjuvant PD-1-blockade

BackgroundAdjuvant immune checkpoint inhibitors (ICI) have improved survival in stage III cutaneous melanoma, yet many patients do not benefit. The tumor microenvironment is pivotal for durable responses; defining cellular composition can pinpoint immune components promoting anti-tumor activity and identify biomarkers associated with improved outcomes.MethodRegional lymph nodes (RLNs) were obtained at surgery from 29 patients with stage III melanoma. Eligible patients received adjuvant anti-PD-1 (αPD-1; pembrolizumab or nivolumab). Mass cytometry (CyTOF) was used to determine cellular composition of pre-treatment surgical specimens. NanoString bulk gene expression data from 125 patients receiving surgery without adjuvant therapy were used to evaluate trends observed in the CyTOF dataset.ResultsHigher proportions of CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cells were associated with improved prognosis in the CyTOF cohort. In the untreated cohort, a “B cell excluded” subgroup (< 2.5% tumor-infiltrating lymphocyte pathology score) had worse outcome, showing reduced B cell score and lower expression of activation genes including CD38, without change in CD8+ T cell score.ConclusionBaseline infiltration of CD8+ TRM and plasmablast-like CD38hiCD19dim cells in RLN is strongly associated with prolonged distant metastasis-free survival in patients receiving αPD-1, supporting their potential as prognostic biomarkers in stage III melanoma.