Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis

J Invest Dermatol. 2016 May;136(5):994-1001. doi: 10.1016/j.jid.2015.12.042. Epub 2016 Jan 29.


Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage. High frequencies of CD45RA(+)CD4(+) and CD3(-)CD56(-) tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8(+)tumor-infiltrated lymphocytes, low level of regulatory T-cell tumor-infiltrated lymphocytes, and low PD-L1 expression on circulating T cells were retained in the multivariate Cox analysis model to predict prolonged overall survival. Prospective studies are needed to determine whether such immunological markers may guide adjuvant therapies in stage III metastatic melanomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Immunophenotyping
  • Immunotherapy / methods
  • Lymph Nodes / pathology*
  • Male
  • Melanoma / mortality*
  • Melanoma / pathology*
  • Melanoma / therapy
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control*
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy
  • Survival Analysis

Supplementary concepts

  • Melanoma, Cutaneous Malignant