GSE144507 Tumor-derived retinoic acid regulates intratumoral monocyte differentiation to promote immune suppression and resistance to immune checkpoint blockade

Contributors : Samir Devalaraja ; Tsun K To ; Ian W Folkert ; Ramakrishnan Natesan ; Zahidul Alam ; Minghong Li ; Yuma Tada ; Konstantin Budagyan ; Mai Dang ; Li Zhai ; Graham P Lobel ; Gabrielle E Ciotti ; T K Eisinger-Mathason ; Irfan A Asangani ; Kristy Weber ; M C Simon ; Malay HaldarSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy. Within solid tumors, why monocytes preferentially differentiate into immunosuppressive tumor associated macrophages (TAMs) but not immunostimulatory dendritic cells (DCs) remains unclear. Using multiple murine sarcoma models, we found that the TME induced retinoic acid (RA) production by tumor cells, which polarized intratumoral monocyte differentiation towards TAMs and away from DCs via suppression of DC-promoting transcription factor Irf4. Genetic inhibition of RA production by tumor cells or pharmacologic inhibition of RA signaling within TME increased stimulatory monocyte-derived cells, enhanced T cell-dependent anti-tumor immunity and demonstrated striking synergy with immune checkpoint blockade. Further, RA responsive gene signature in human monocytes correlated with an immunosuppressive TME in multiple human tumors. RA has been long considered as an anti-cancer agent, but our work demonstrates its tumorigenic capability via myeloid-mediated immune suppression and provides proof of concept for targeting this pathwa...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

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AbstractEpigenetic processes are essential for normal development and the maintenance of tissue-specific gene expression in mammals. Changes in gene expression and malignant cellular transformation can result from disruption of epigenetic mechanisms, and global disruption in the epigenetic landscape is a key feature of cancer. The study of epigenetics in cancer has revealed that human cancer cells harbor both genetic alterations and epigenetic abnormalities that interplay at all stages of cancer development. Unlike genetic mutations, epigenetic aberrations are potentially reversible through epigenetic therapy, providing a ...
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
Contributors : Samir Devalaraja ; Tsun K To ; Ian W Folkert ; Ramakrishnan Natesan ; M Z Alam ; Minghong Li ; Yuma Tada ; Konstantin Budagyan ; Mai Dang ; Li Zhai ; Graham P Lobel ; Gabrielle E Ciotti ; T S Eisinger-Mathason ; Irfan A Asangani ; Kristy Weber ; M C Simon ; Malay HaldarSeries Type : Expression profiling by arrayOrganism : Mus musculusThe microenvironment has profound effect on macrophage phenotype. Here we examine the phenotype of macrophages infiltrating murine undifferentiated pleomorphic sarcomas. We used microarray to examine gene expression profile of tumor-associated macrophages in murine undifferentia...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
Contributors : Samir Devalaraja ; Tsun K To ; Ian W Folkert ; Ramakrishnan Natesan ; M Z Alam ; Minghong Li ; Yuma Tada ; Konstantin Budagyan ; Mai Dang ; Li Zhai ; Graham P Lobel ; Gabrielle E Ciotti ; T S Eisinger-Mathason ; Irfan A Asangani ; Kristy Weber ; M C Simon ; Malay HaldarSeries Type : Expression profiling by arrayOrganism : Mus musculusRetinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in mouse monocytes.The immunosuppressive tumor microenvironment (TME) is a major barrier ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
Contributors : Samir Devalaraja ; Tsun K To ; Ian W Folkert ; Ramakrishnan Natesan ; M Z Alam ; Minghong Li ; Yuma Tada ; Konstantin Budagyan ; Mai Dang ; Li Zhai ; Graham P Lobel ; Gabrielle E Ciotti ; T S Eisinger-Mathason ; Irfan A Asangani ; Kristy Weber ; M C Simon ; Malay HaldarSeries Type : Expression profiling by arrayOrganism : Homo sapiensRetinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in human monocytes.The immunosuppressive tumor microenvironment (TME) is a major barrier ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
This article discusses the progression of surgical treatment of malignant bone cancers.
Source: Nursing Clinics of North America - Category: Nursing Authors: Source Type: research
AbstractSoft tissue sarcomas (STSs) are heterogeneous cancers associated with poor prognosis due to high rates of local recurrence and metastasis. The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor-infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction have been established as effective anti-cancer drugs. However, studies on the PD-L1 and PD-1 expression status in STS are commonly limited by small sample size, analysis of single STS subtypes, or lac...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
ConclusionThe immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Authors: Ayodele O, Razak ARA Abstract Soft-tissue sarcoma (sts) is a rare mesenchymal malignancy that accounts for less than 1% of all adult tumours. Despite the successful advancement of localized therapies such as surgery and radiotherapy, these tumours can, for many, recur-often with metastatic disease. In the advanced setting, the role of systemic therapies is modest and is associated with poor survival. With the discovery of immunotherapies in other tumour types such as melanoma and lung cancer, interest has been renewed in exploring immunotherapy in sts. The biology of some stss makes them ripe for immunothe...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Ingley KM, Cohen-Gogo S, Gupta AA Abstract Soft-tissue sarcoma (sts) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (rms) is most prevalent in children less than 10 years of age and peaks again during adolescence (16-19 years of age). Multi-agent chemotherapy constitutes the mainstay of treatment for rms. In other non-rhabdomyosarcoma soft-tissue tumours, such as synovial sarcoma, evidence for routine use of chemotherapy is less robust, and alternative treatment options, including targeted agents and immunotherapy, are being exp...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Patients with metastatic thyroid cancer (mTC) have limited options for effective therapies. Tyrosine kinase inhibitors (TKIs) remain the mainstay of treatment, often at the expense of significant systemic side effects without a proven survival benefit. The use of immunotherapy has revolutionized the treatment of cancer, however, its specific utility in mTC is not yet known.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Non-squamous Cell Malignancies of the Head and Neck: thyroid, sarcomas, skin cancers, salivary gland and sinus cancers Source Type: research
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