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• W4376869979 abstract "Tumor microenvironment (TME) is a heterogeneous system consisting of both cellular and acellular components. The growth and progression of tumors rely greatly on the nature of TME, marking it as an important target in cancer immunotherapy. Lewis Lung Carcinoma (LLC) is an established murine lung cancer model representing immunologically ‘cold’ tumors characterized by very few infiltrated cytotoxic T-cells, high levels of Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs). Here, we report various strategies we applied to reverse the non-immunogenic character of this cold tumor by imparting: a) immunogenic cell death using Hypericin nanoparticle-based photodynamic therapy (PDT), b) repolarising TAM using a TLR7/8 agonist, resiquimod, c) immune checkpoint inhibition using anti-PD-L1 and d) depleting MDSCs using low-dose 5-fluorouracil (5-FU) chemotherapy. Interestingly, the nano-PDT, resiquimod or anti-PD-L1 treatment had no major impact on tumor growth, whereas low-dose 5-FU-mediated depletion of MDSCs showed significant anti-tumor effect, primarily caused by the increased infiltration of CD8+ cytotoxic T-cells (∼96%). Though we have tested combining PDT with resiquimod or 5-FU for any synergistic effect, low-dose 5-FU alone showed better response than combinations. In effect, we show that depletion of MDSCs using low-dose 5-FU was one of the best methods to augment infiltration of CD8+ cytotoxic T-cells into a cold tumor, which is resistant to conventional therapies including immune checkpoint inhibitors." @default.
• W4376869979 created "2023-05-18" @default.
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• W4376869979 date "2023-07-01" @default.
• W4376869979 modified "2023-10-14" @default.
• W4376869979 title "5-FU mediated depletion of myeloid suppressor cells enhances T-cell infiltration and anti-tumor response in immunotherapy–resistant lung tumor" @default.
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• W4376869979 doi "https://doi.org/10.1016/j.intimp.2023.110129" @default.
• W4376869979 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37201402" @default.
• W4376869979 hasPublicationYear "2023" @default.
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