slanDCs selectively accumulate in carcinoma-draining lymph nodes and marginate metastatic cells (original) (raw)
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slanDCs in carcinoma-draining lymph nodes
OncoImmunology, 2014
Dendritic cells (DCs) are known to initiate adaptive immune responses against malignant cells. however, the role in anticancer immunosurveillance of 6-sulfo LacNAc-expressing DCs (slanDCs), a distinct population of circulating and tissue-resident pro-inflammatory DCs, is unclear. we have recently demonstrated the involvement of slanDCs in nodal immune responses against carcinoma cells.
Immunology Letters, 2002
Dendritic cells (DCs) are bone-marrow derived 'professional' antigen presenting cells (APC). They are considered as the most potent APC able to induce primary immune responses. DC efficiently capture and process proteic and non-proteic antigens. They are widely distributed throughout the body and occupy sentinel positions such as epithelia. Establishment of an immune response against cancer may depend of the capacity of DCs to transfer (to capture, to process and to present) tumor antigens into regional lymph nodes where they can induce a specific response leading to tumor rejection. Because host 'professional' DCs are one of the most important elements in the induction of specific anti-tumor responses and lymph nodes are the places where the immune response takes place, we investigated the densities of DCs within regional metastasis-free lymph nodes from 47 patients with different malignant epithelial tumors as comparing with lymph nodes from 11 patients without malignancies using an immunohistochemistry method with anti-S100 protein, CD86 and CD1a antibodies. By means of morphometric analysis, we observed that S100'/ and CD1a'/ DCs densities in regional lymph nodes from cancer patients were significatively decreased as compared with control lymph nodes (P B/0.0001 and 0.003, respectively). S100'/ DCs and CD86'/ DCs densities in lymph nodes draining cancer were similar. Taken together, these data indicated that lymph nodes draining cancer had significantly less CD1a'/ DCs than S100'/ and possibly CD86'/ DCs. These findings may represent another mechanism by which tumors evade the immune recognition. #
Cancer Research, 2014
Tumor-infiltrating T cells, particularly CD45RO þ CD8 þ memory T cells, confer a positive prognostic value in human cancers. However, the mechanisms that promote a protective T-cell response in the tumor microenvironment remain unclear. In chronic inflammatory settings such as the tumor microenvironment, lymphoid neogenesis can occur to create local lymph node-like structures known as tertiary lymphoid structures (TLS). These structures can exacerbate a local immune response, such that TLS formation in tumors may help promote an efficacious immune contexture. However, the role of TLS in tumors has yet to be investigated carefully. In lung tumors, mature dendritic cells (DC) present in tumor-associated TLS can provide a specific marker of these structures. In this study, we evaluated the influence of TLS on the characteristics of the immune infiltrate in cohorts of prospective and retrospective human primary lung tumors (n ¼ 458). We found that a high density of mature DC correlated closely to a strong infiltration of T cells that are predominantly of the effector-memory phenotype. Moreover, mature DC density correlated with expression of genes related to T-cell activation, T-helper 1 (Th1) phenotype, and cytotoxic orientation. Lastly, a high density of TLS-associated DC correlated with long-term survival, which also allowed a distinction of patients with high CD8 þ T-cell infiltration but a high risk of death. Taken together, our results show how tumors infiltrated by TLS-associated mature DC generate a specific immune contexture characterized by a strong Th1 and cytotoxic orientation that confers the lowest risk of death. Furthermore, our findings highlight the pivotal function of TLS in shaping the immune character of the tumor microenvironment, in promoting a protective immune response mediated by T cells against cancer. Cancer Res; 74(3); 1-11. Ó2013 AACR.
Nature communications, 2016
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8(+) T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vacci...
Role of dendritic cells in progression and clinical outcome of colon cancer
International Journal of Colorectal Disease, 2012
Purpose The dendritic cells (DCs) are key players in the initiation and regulation of immune responses including antitumor immunity. In the current study, we aimed to elucidate the role of different subtypes of DCs infiltrating the tumor stroma and invasive margin for tumor progression and survival of patients with colon cancer.
A novel dendritic cell subset involved in tumor immunosurveillance
Nature Medicine, 2006
The interferon (IFN)-c-induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice 1,2 . Here we show that the main source of IFN-c is not the conventional NK cell but a subset of B220 + Ly6Cdendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220 + NK1.1 + dendritic cells secrete high levels of IFN-c and mediate TRAIL-dependent lysis of tumor cells. Adoptive transfer of these IFN-producing killer dendritic cells (IKDCs) into tumorbearing Rag2 -/-Il2rg -/mice prevented tumor outgrowth, whereas transfer of conventional NK cells did not. In conclusion, we identified IKDCs as pivotal sensors and effectors of the innate antitumor immune response.
Journal for ImmunoTherapy of Cancer, 2019
Background: Immune regulated pathways influence both breast cancer (BrC) development and response to (neo) adjuvant chemotherapy. The sentinel lymph node (SLN), as the first metastatic site, is also the first site where BrCinduced suppression of immune effector subsets occurs. Since intricate knowledge of the phenotypic and functional status of these immune effector subsets is lacking, we set out to map the immune landscape of BrC SLN. Methods: Viable LN cells from BrC SLN (n = 58) were used for detailed flowcytometry-assisted mapping of the immune landscape of BrC SLN in a comparative analysis with healthy (i.e. prophylactic mastectomy-derived) axillary lymph nodes (HLN, n = 17). Findings were related to clinicopathological characteristics. Results: Our data show that BrC-induced immune suppression in tumor-involved SLN, as evidenced by increased Treg and MDSC rates as well as by a generalized state of T cell anergy, coincides with hampered activation of LN-resident (LNR) dendritic cell (DC) subsets rather than of migratory DC subsets. Importantly, suppression of these LN-resident DC subsets preceded profoundly disabled T cell effector functions in tumor-involved SLN. Furthermore, we provide evidence that the suppressed state of LNR-cDC is not only related to nodal involvement but is also related to high-risk breast cancer subtypes that lack expression of hormone receptors and may be a negative predictor of disease-free survival. Conclusion: These data thus provide new insights in the mechanisms underlying loco-regional immune suppression induced by BrC and how these relate to clinical outcome. They identify the LNR-cDC subset as a pivotal regulatory node in cellular immune suppressive pathways and therefore as a promising therapeutic target to combat immune suppression and secure the induction of effective antitumor immunity, e.g. in combination with neo-adjuvant chemotherapy.
OncoImmunology, 2015
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. Tumorinfiltrating 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.