Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDCs) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex-vivo from a large cohort of melanoma patients and in-vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting pro-inflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of IL5-, IL13- and IL10-producing T cells in melanoma patients correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22 and MMP2 found in melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation or/and early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities.
- Received August 6, 2013.
- Revision received September 12, 2013.
- Accepted September 20, 2013.
- Copyright © 2013, American Association for Cancer Research.