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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [DASAITC]

ABSTRACT: Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [DASAITC]

PROVIDER: PRJNA1266224 | ENA |

REPOSITORIES: ENA

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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy

Project description:Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy

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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [shYES1]

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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [PD1CTLA4]

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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [DASAITC]

Project description:Effective strategies to reinvigorate the immune system are needed to improve outcomes in small cell lung cancer (SCLC). Targeting Src family kinases with dasatinib (Dasa) can elicit immunomodulatory effects in some cancer types. Here, we explored the potential of combining Dasa with immune checkpoint blockade in SCLC. While the SCLC models were refractory to anti-PD-1 or anti-CTLA4 monotherapy, anti-PD-1 and anti-CTLA4 combination immunotherapy (ITc) induced a significant antitumor response. Further, the Dasa+ITc combination was superior to ITc or Dasa alone. Dasa+ITc activity was mediated by CD4+ T cells, MHC-II+ antigen presenting cells (APCs), and natural killer (NK) cells, as depletion of these populations impeded the combination treatment antitumor efficacy. Increased tumor infiltration of CD4+ and CD8+ T cells, NK cells, M1-like macrophages, and CD11c+ APCs and a reduction of regulatory T cells (Tregs) and M2-like macrophages were found in Dasa+ITc-treated mice. Dasa increased CCL5 in NK cells and reduced Treg cell conversion from CD4+ lymphocytes. Dasa+ITc therapy elicited robust antitumor efficacy in 3D co-cultures of immune and SCLC cells. In vivo experiments showed that CCL5 was necessary for the Dasa+ITc response. In SCLC immunotherapy-treated patients, a gene signature including CD4, CIITA, and tumor mutational burden predicted good prognosis. On-treatment CCL5 plasma levels were increased only in patients with long progression-free survival, and pre-treatment secretomics identified cytokines related to myeloid cells significantly associated with poor prognosis. In summary, combining Dasa with immunotherapy represents a strategy to treat SCLC, with CCL5 as a cytokine that could serve to monitor response.

2025-07-17 | GSE297817 | GEO

Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy [shYES1]

2025-07-17 | GSE297846 | GEO

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Chemohormonal Therapy Remodels Prostate Cancer Immune Microenvironment and Enhances Checkpoint Inhibitor-based immunotherapy

Project description:Checkpoint blockade immunotherapy is a promising strategy in cancer treatment, depending on a favorable preexisting tumor immune microenvironment. However, prostate cancer is usually considered as an immune “cold” tumor with the poor immunogenic response and low density of tumor-infiltrating immune cells. This research uses samples from prostate cancer patients showing that docetaxel-based chemohormonal therapy reprograms the immune microenvironment and increases tumor-infiltrating T cells. Mechanistically, docetaxel treatment activates the cGAS/STING pathway and induces the type I interferon signaling, which may boost T cell-mediated immune response. In a murine prostate cancer model, chemohormonal therapy sensitizes tumor-bearing mice to PD1-blockade therapy. These findings demonstrate that docetaxel-based chemohormonal therapy activates prostate cancer immunogenicity and acts cooperatively with anti-PD-1 checkpoint blockade, providing a combination immunotherapy strategy that would lead to better therapeutic benefit for prostate cancer.

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Project description:Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy

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Dasatinib Remodels the Tumor Microenvironment and Sensitizes Small Cell Lung Cancer to Immunotherapy

Project description:This SuperSeries is composed of the SubSeries listed below.

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Chemohormonal Therapy Remodels Prostate Cancer Immune Microenvironment and Enhances Checkpoint Inhibitor-based immunotherapy

Project description:Chemohormonal Therapy Remodels Prostate Cancer Immune Microenvironment and Enhances Checkpoint Inhibitor-based immunotherapy

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