slanDCs selectively accumulate in carcinoma-draining lymph nodes and marginate metastatic cells

Abstract

Dendritic cells (DCs) initiate adaptive immune responses to cancer cells by activating naive T lymphocytes. 6-sulfo LacNAc þ DCs (slanDCs) represent a distinct population of circulating and tissue proinflammatory DCs, whose role in cancer immune surveillance is unknown. Herein, by screening a large set of clinical samples, we demonstrate accumulation of slanDCs in metastatic tumour-draining lymph nodes (M-TDLN) from carcinoma patients. Remarkably, slanDCs are absent at the primary carcinoma site, while their selective nodal recruitment follows the arrival of cancer cells to M-TDLN. slanDCs surround metastatic carcinoma deposits in close proximity to dead cells and efficiently phagocytose tumour cells. In colon carcinoma patients, the contingent of circulating slanDCs remains intact and competent in terms of IL-12p70 and tumour necrosis factor alpha production, induction of T-cell proliferation and migratory capacity to a set of chemokines produced in M-TDLN. We conclude that activated slanDCs represent previously unrecognized players of nodal immune responses to cancer cells.

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

“…[19][20][21][22][24][25][26] More recently, Vermi et al demonstrated that slanDCs are numerous in metastatic tumor-draining lymph nodes from cancer patients. 28,29 Following these findings, indicating that slanDCs may play an important role in antitumor immunity, we explored the presence of this distinct human DC subset in RCC tissues. slanDCs were preferentially located on the perimeter of tumor nests in close proximity to tumor cells within most metastatic tumor-draining lymph nodes.…”

Social networking of human neutrophils within the immune system

“…113 In this context, we have shown that metastatic tumor-draining lymph nodes from carcinoma patients infiltrated by slanDCs also contain, in some cases, CD66b 1 neutrophils within an immunosuppressed like microenvironment. 114 A very recent observation in a head and neck cancer model suggests that neutrophils, previously exposed to tumor-conditioned medium, induce an invasive, NK-resistant, and highly metastatic tumor cell phenotype (S. Brandau, unpublished data, 2014). Another mechanism proposed to explain protumor activities by human and mouse tumor-associated neutrophils consists in their ability to recruit regulatory T cells (Tregs) to the tumor sites, via CCL17 release.…”

Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing

“…In order to test the specificity of FDCSP and SRGN in FDC-S diagnosis we stained 87 soft tissue tumors, 5 thymomas, 5 melanomas (Supplementary Table 3), 3 interdigitating dendritic cell sarcomas and 114 carcinomas [24]. FDCSP was expressed by two soft tissue tumors, one sinonasal haemangiopericytoma (SNHP-1) and one synovial sarcoma (SS-2); SRGN was negative in all (Supplementary Table 4).…”

“…In order to further confirm their specificity, FDCSP and SRGN were additionally applied on TMAs including 114 carcinomas of different origin, previously described [24], and on whole tissue sections of 28 additional control cases (control group #2, Supplementary Table 3). Antibodies applied are detailed in Supplementary Table 5.…”