The immune escape in melanoma: role of the impaired dendritic cell function

Abstract

Melanoma is an immunogenic cancer that overcomes the control of the immune system through the production of tolerogenic cytokines and growth factors in the microenvironment. In melanoma, dendritic cells (DC) show severe alterations in maturation, cross-priming and antigenic presentation, while other accessory cells infiltrating the tumor milieu also suppress DCs through the activation of the STAT pathway by IL-10 and IL-6. Novel immunotherapy strategies blocking cytotoxic T-lymphocyte antigen (CTLA-4) are successful in advanced disease, while melanoma cells carrying the BRAF^V600E mutation further reinforce the immune suppression by activating MAPKs. Here, we review the major mechanisms involved in the cross-talk between melanoma cells and the immune system as well as the issue of defects in DCs in relation to novel studies aimed at restoring their anti-tumor activity.

Keywords::

• dendritic cells
• melanoma
• microenvironment
• STAT
• Treg cells

Financial & competing interests disclosure

This work was funded by a grant (# IG11647) from AIRC (Italian Association for Cancer Research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Melanoma is the result of defective interplay between tumor cells and dendritic cells (DCs).

• DC impairment is critical for melanoma progression.

• Other populations infiltrate the tumor microenvironment, including Treg cells and MDSCs.

• The overproduction of soluble factors and activation of the STAT-dependent kinases promote the defective immune response in melanoma.

• Targeting cytotoxic T-lymphocyte antigen (CTLA)-4 expressed by T-cells restores the cross-talk with DCs and show great impact on overall survival in patients with advanced disease.

• Mutations of BRAF apparently affect the efficiency of DC priming.

• New pathways need to be investigated, and therapeutic combinations in patients with metastatic melanoma are of great effort in terms of response rate and progression-free survival.

Notes