Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis

Abstract

Dendritic cells (DCs) essentially contribute to the induction and regulation of innate and adaptive immunity. Based on these important properties, DCs may profoundly influence tumor progression in patients. However, little is known about the role of distinct human DC subsets in primary tumors and their impact on clinical outcome. In the present study, we investigated the characteristics of human 6-sulfo LacNAc (slan) DCs in clear cell renal cell carcinoma (ccRCC). slanDCs have been shown to display various tumor-directed properties and to accumulate in tumor-draining lymph nodes from patients. When evaluating 263 ccRCC and 227 tumor-free tissue samples, we found increased frequencies of slanDCs in ccRCC tissues compared to tumor-free tissues. slanDCs were also detectable in the majority of 24 metastatic lymph nodes and 67 distant metastases from ccRCC patients. Remarkably, a higher density of slanDCs was significantly associated with a reduced progression-free, tumor-specific or overall survival of ccRCC patients. Tumor-infiltrating slanDCs displayed an immature phenotype expressing interleukin-10. ccRCC cells efficiently impaired slanDC-induced T-cell proliferation and programming as well as natural killer (NK) cell activation. In conclusion, these findings indicate that higher slanDC numbers in ccRCC tissues are associated with poor prognosis. The induction of a tolerogenic phenotype in slanDCs leading to an insufficient activation of innate and adaptive antitumor immunity may represent a novel immune escape mechanism of ccRCC. These observations may have implications for the design of therapeutic strategies that harness tumor-directed functional properties of DCs against ccRCC.

Quantitative and functional alterations of 6-sulfo LacNac dendritic cells in multiple myeloma

“…Thus, it has been demonstrated that Slan-DCs are numerous in metastatic tumor-draining lymph nodes from carcinoma patients, and that Slan-DCs accumulate in renal carcinoma. 13,14 Here, we show that the number of Slan-DCs is decreased in the PB of MM patients as compared to healthy donors and to MGUS patients. Moreover, we observed that the number of Slan-DCs increases with tumor load, suggesting that these cells can play a role in MM pathophysiology.…”

“…For instance, in renal cancer, their phenotype is impacted by the neoplastic cells which make them tolerogenic. 13 In contrast, in colon carcinoma, the contingent of circulating Slan-DCs remains normal as well as their inflammatory properties. 14 Moreover, Slan-DCs exhibit a remarkable plasticity in terms of phenotype which may depend on the local tissue they infiltrate.…”

Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis

“…SlanMo were shown in vitro to differentiate into proinflammatory DCs (13,15,69) or macrophages (14) depending on the local microenvironment. Similarly, in vivo slanMo were identified as IL-23-producing inflammatory dermal DCs in psoriasis (16), as DCs in tonsils (14), or as immature IL-10-producing macrophage-like cells in renal cell carcinoma (70).…”

Phenotype, Function, and Mobilization of 6-Sulfo LacNAc-Expressing Monocytes in Atopic Dermatitis

“…Subsequently, a role for slan + cells was found in lupus skin lesions as well as in several other organs or diseases such as in multiple sclerosis, Crohn’s disease, rheumatoid arthritis, or HIV ( 16 – 20 ). Although slan + cells can clearly function as DCs, they may also differentiate into macrophages, as demonstrated in renal cell carcinoma ( 17 , 19 ).…”