コンテンツへスキップ
Merck
  • Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL.

Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL.

Cancer immunology research (2014-04-30)
Caroline Aspord, Marie-Therese Leccia, Julie Charles, Joel Plumas
要旨

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 (pDC) 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 proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13- and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or 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.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
ホルボール 12-ミリスタート 13-アセタート, ≥99% (TLC), film or powder
Sigma-Aldrich
ホルボール 12-ミリスタート 13-アセタート, for use in molecular biology applications, ≥99% (HPLC)
Sigma-Aldrich
ピルビン酸ナトリウム, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
ピルビン酸ナトリウム, ReagentPlus®, ≥99%
Sigma-Aldrich
ホルボール 12-ミリスタート 13-アセタート, synthetic, ≥98.0% (TLC)
Sigma-Aldrich
ピルビン酸ナトリウム, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
ピルビン酸ナトリウム, BioXtra, ≥99%
Sigma-Aldrich
ピルビン酸ナトリウム, Hybri-Max, powder, suitable for hybridoma
Sigma-Aldrich
ピルビン酸ナトリウム, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
Sigma-Aldrich
ピルビン酸ナトリウム, SAJ special grade, ≥95.0%