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

Background Adjuvant 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. Method Regional 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. Results Higher proportions of CD103 + PD-1 + CD8 + (T RM ) T cells and plasmablast-like CD38 hi CD19 dim 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. Conclusion Baseline infiltration of CD8 + T RM and plasmablast-like CD38 hi CD19 dim 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.