In Brief: Myeloid-derived suppressor cells in cancer.

The role of myeloid-derived suppressor cells (MDSCs) in cancer development has become clear over recent years, and MDSC targeting is an emerging opportunity for enhancing the effectiveness of current anticancer therapies. As MDSCs are not only able to limit anti-tumour T-cell responses, but also to promote tumour angiogenesis and invasion, their monitoring has prognostic and predictive value. Herein, we review the key features of MDSCs in cancer promotion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab.

Ipilimumab, the first immune-checkpoint inhibitor extending overall survival (OS) in metastatic melanoma patients, has a survival benefit only in a proportion of patients and the development of reliable predictive biomarkers is still an unmet need. To meet this request, we used a multivariate statistical approach to test whether myeloid-derived suppressor cells (MDSC) or other tumor-associated and immunological parameters may serve as predictive or prognostic biomarkers in melanoma patients receiving ipilimumab. By using a standardized approach to determine the circulating levels of four MDSC subsets, we observed a significant expansion of three MDSC subsets at baseline, as compared to controls and, upon treatment, that high levels of CD14+/IL4Rα+ MDSCs were an independent prognostic factor of reduced OS. On the contrary, longer OS was associated to low levels of the proinflammatory proteins IL-6 and CRP and tumor-associated factors S100B and LDH both at baseline and after treatment. Increasing number of total T cells and especially of PD-1+/CD4+ T cells were associated with better prognosis, and upregulation of PD-1+ expression on CD4+ T cells upon treatment was associated with lower toxicity. As several parameters were associated to OS, we included these factors in a multivariate survival model, and we identified IL-6 and ECOG PS as independent biomarkers associated with improved OS, whereas high levels of LDH and CD14+/IL4Rα+ MDSCs were negative independent markers of reduced OS.