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Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associates with T cell abundance. Altering Wnt1 expression profoundly affects growth of murine lung adenocarcinomas and this is dependent on conventional dendritic cells (cDCs) and T cells. Mechanistically, Wnt1 leads to transcriptional silencing of CC/CXC chemokines in cDCs, T cell exclusion and cross-tolerance. Wnt-target genes are up-regulated in human intratumoral cDCs and decrease upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-nanoparticles given as single therapy or part of combinatorial immunotherapies act at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 induces immunologically cold tumors through cDCs and highlight its immunotherapeutic targeting.
This article was published in the following journal.
Name: Nature communications
Dendritic cells are a specialized type of antigen-presenting cell that bridges both innate and adaptive immune system function. While much is understood about dendritic cells and their role in the imm...
Exposure to MNP generates Th2 response-inducing dendritic cells. Transfer of OVA/MNP-primed dendritic cells induces nasal allergy. Inhibition of Bcl2L12 prevents nasal allergy development.
Gastric dendritic cells (DCs) control the adaptive response to infection with Helicobacter pylori, a major risk factor for peptic ulcer disease and gastric cancer. We hypothesize that DC interactions ...
Intradermal (i.d.) application of vaccine is promising way how to induce specific immune response against particular pathogens. Adjuvants, substances added into vaccination dose with the aim to increa...
In our research, we aimed to investigate the roles of CC-chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major-infected human dendritic cells (DCs).
Malignant mesothelioma is an aggressive pleural disease, related to asbestos exposure. At present, cytotoxic chemotherapy is the only evidence based treatment for the disease, but efficacy...
A Study of Type-1 Polarized Dendritic Cell (αDC1) Vaccine in Combination With Tumor-Selective Chemokine Modulation (Interferon-α2b, Rintatolimod, and Celecoxib) in Subjects With Chemo-Refractory Metastatic Colorectal Cancer
The investigators hypothesize that the treatment of metastatic colorectal cancer (mCRC) patients with the combination of alpha-type-1-polarized dendritic cell (αDC1) vaccines and tumor-se...
The study induces an immune response towards the stem-cell like part of glioblastomas in combination with standard therapy. The aim is to define and characterize the feasibility, potential...
To define the safety and efficacy of sibling-supplied, HIV antigen-pulsed dendritic cells in increasing the immune response in HIV-infected patients. Dendritic cells are a type of white b...
This study investigates the use of the patients own immune cells to treat prostate cancer. Cells are taken from the patient and grown in the laboratory to become specialized immune cells c...
A CXCR6 receptor-binding chemokine that functions as a scavenger receptor for oxidized low density lipoprotein (OxLDL) when expressed by MACROPHAGES. Its secreted, or cytokine form induces a strong chemotactic response for MONOCYTES when it is expressed by DENDRITIC CELLS.
A CC-type chemokine highly expressed in the lungs, lymph nodes, placenta, and bone marrow; it is also expressed by DENDRITIC CELLS in the GERMINAL CENTER, and peripheral blood MACROPHAGES. It functions as a chemotactic factor that specifically attracts LYMPHOCYTES, especially B-Cells, into lymph node follicles, and naive T-cells towards dendritic cells and activated T-cells. It does not attract MONOCYTES or GRANULOCYTES.
A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes.
CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.
A CC-type chemokine that is found at high levels in the THYMUS and has specificity for CCR4 RECEPTORS. It is synthesized by DENDRITIC CELLS; ENDOTHELIAL CELLS; KERATINOCYTES; and FIBROBLASTS.
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...