Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer

Szpor, Joanna; Streb, Joanna; Glajcar, Anna; Frączek, Paulina; Winiarska, Aleksandra; Tyrak, Katarzyna Ewa; Basta, Paweł; Okoń, Krzysztof; Jach, Robert; Hodorowicz-Zaniewska, Diana

doi:10.3390/diagnostics11040702

Cited by 39 publications

(28 citation statements)

References 40 publications

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“…We identified a large population of macrophages, including those associated with tumors (primary or liver mets) or with normal tissue (normal colon or liver). We also identified a number of other myeloid dendritic cell (DC) types, including BATF3+ DCs required for effector T cell trafficking and adoptive T cell therapy 25 , CD1c+ DCs which prime cytotoxic T cell responses 26 , Tumor-associated LAMP3+ DCs 27,28 , and LILRA4+ plasmacytoid dendritic cells 29 .…”

Section: Resultsmentioning

confidence: 99%

Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment

Zhu

Tian

et al. 2022

Preprint

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SummaryThe initiation and progression of cancer are inextricably linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorectal cancers (CRCs) and mouse CRC models, ask how these interactions are altered in established, long-term human tumor organoid (tumoroid) cultures, and functionally recapitulate human myeloid-carcinoma interactions in vitro. Tumoroid cultures suppress gene expression programs involved in promoting inflammation and immune cell migration through receptor-ligand interactions, providing a reductive platform for re-establishing carcinoma-immune cell interactions in vitro. Introduction of human monocyte-derived macrophages into tumoroid cultures instructs macrophages to acquire pro-tumorigenic gene expression programs similar to those observed in vivo. This includes hallmark induction of SPP1, encoding Osteopontin, an extracellular CD44 ligand with established oncogenic effects. Taken together, these findings offer a framework for understanding CRC-TME interactions and provide a reductionist tool for modeling specific aspects of these interactions.

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Section: Resultsmentioning

confidence: 99%

Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment

Zhu

Tian

et al. 2022

Preprint

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“…In contrast, higher densities of CD1a+ DCs both in the stroma of primary invasive tumors and in LNs were associated with absence of nodal metastases and good prognosis [ 22 , 23 ]. Similarly, in our recent study we showed that a higher density of intratumoral CD1a DCs was associated with longer progression-free survival in BC patients [ 16 ]. These would support the hypothesis that higher levels of DCs evoke functional anti-cancer responses [ 22 ].…”

Section: Discussionmentioning

confidence: 61%

“…Recently we have shown that the content of respective DCs subtypes in BC tumors differs according to BC molecular subtype and clinicopathological features [ 16 ]. In this study, we investigated the densities of several DC populations in SLNs of invasive breast cancer patients with respect to the size of nodal metastasis and other prognostic parameters in this malignancy.…”

Section: Introductionmentioning

confidence: 99%

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden

Szpor

Streb

Glajcar

et al. 2022

IJMS

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BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

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“…In agreement with their anti-tumor potentials, a higher density of tumor-infiltrating cDCs is associated with a better prognosis for patients with various tumor types [ 35 – 37 ]. Here we evaluated the anti-tumor activities of several DC-targeting chemokines in parallel to explore the possibility of using them for immunotherapy.…”

Section: Discussionmentioning

confidence: 95%

Dendritic cell-targeting chemokines inhibit colorectal cancer progression

Yuan

Zhou

Wang

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

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Aim: Recent progress in cancer immunotherapy has shown its promise and prompted researchers to develop novel therapeutic strategies. Dendritic cells (DCs) are professional antigen-presenting cells crucial for initiating adaptive anti-tumor immunity, therefore a promising target for cancer treatment. Here, anti-tumor activities of DC-targeting chemokines were explored in murine colorectal tumor models. Methods: The correlation of chemokine messenger RNA (mRNA) expression with DC markers was analyzed using The Cancer Genome Atlas (TCGA) dataset. Murine colorectal tumor cell lines (CT26 and MC38) stably overexpressing mouse C-C motif chemokine ligand 3 (CCL3), CCL19, CCL21, and X-C motif chemokine ligand 1 (XCL1) were established by lentiviral transduction. The effect of chemokines on tumor cell proliferation/survival was evaluated in vitro by cell counting kit-8 (CCK-8) assay and colony formation assay. Syngeneic subcutaneous tumor models were used to study the effects of these chemokines on tumor growth. Ki-67 expression in tumors was examined by immunohistochemistry. Immune cells in the tumor microenvironment (TME) and lymph nodes were analyzed by flow cytometry. Results: Expression of the four chemokines was positively correlated with the two DC markers [integrin alpha X (ITGAX) and CLEC9A] in human colorectal tumor samples. Tumoral overexpression of DC-targeting chemokines had little or no effect on tumor cell proliferation/survival in vitro while significantly suppressing tumor growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that CCL19, CCL21, and XCL1 boosted the ratios of DCs and T cells in CD45+ leukocytes while CCL3 increased the percentage of CD45+ leukocytes in total cells in MC38 tumor. XCL1 had an additional positive effect on antigen uptake by DCs in the TME and antigen transfer to tumor-draining lymph nodes. Conclusions: CCL3, CCL19, CCL21, and XCL1 exhibited potent anti-tumor activities in vivo, although they might differentially regulate immune cells in the TME and antigen transfer to lymph nodes.

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Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer

Cited by 39 publications

References 40 publications

Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment

Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden

Dendritic cell-targeting chemokines inhibit colorectal cancer progression

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