Myeloid-derived suppressor cells predict survival of advanced melanoma patients: comparison with regulatory T cells and NY-ESO-1- or Melan-A-specific T cells
Menée sur 94 patients atteints de mélanome avec métastases distantes, puis validée sur une cohorte de 39 autres patients, cette étude compare, du point de vue de la survie, la valeur pronostique des cellules myéloïdes suppressives, des cellules T régulatrices et des cellules T spécifiques de l'antigène tumoral NY-ESO-1 ou de l'antigène Melan A
PURPOSE : To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) compared to functional tumor- antigen-specific T cells in melanoma patients with distant metastasis.
EXPERIMENTAL DESIGN : The percentage of CD14+CD11b+HLA-DR-/low MDSCs, CD4+CD25+FoxP3+ Tregs and the presence of NY-ESO-1- or Melan-A-specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan-Meier and log rank tests. Multivariate analyses were performed using Cox regression models.
RESULTS : NY-ESO-1-specific T cells, the M-category and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1-specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of >11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months vs. 8 months for others (p<0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma-antigen-specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs.
CONCLUSIONS : Circulating CD14+CD11b+HLA-DR-/low MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen-specific T cells in advanced melanoma patients. Our findings provide a rationale to investigate MDSCs-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell-transfer approaches.
Clinical Cancer Research , résumé, 2013