2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03C.02 The Potential of Fluoropyrimidine to be an Immunologically Optimal Partner of Immunotherapy for Thoracic Malignancies

EP.03C.02 The Potential of Fluoropyrimidine to be an Immunologically Optimal Partner of Immunotherapy for Thoracic Malignancies

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The study presented at the IASLC 2024 World Conference on Lung Cancer investigates the potential of fluoropyrimidine, specifically 5-fluorouracil (5-FU) and its oral formulation S-1, as immune-enhancing partners with immune checkpoint inhibitors (ICIs) for treating thoracic malignancies. Traditionally, chemotherapy drugs like pemetrexed and taxanes are combined with ICIs, but their immunological compatibility hasn't been fully understood. This research explores whether fluoropyrimidine might be a more optimal partner due to its unique immune-modulating effects.<br /><br />Using several human non-small cell lung cancer (NSCLC) and murine mesothelioma cell lines, researchers evaluated the induction of immunogenic cell death (ICD) and the reduction of myeloid-derived suppressor cells (MDSCs) by various chemotherapeutic agents. The study found that 5-FU was particularly effective at inducing ICD, as indicated by an increased expression of calreticulin (CRT) and ATP secretion, even more so when combined with platinum. Tumor cells treated with 5-FU in mouse models initiated a strong anti-tumor immune response due to the enhanced depletion of MDSCs, potentially by suppressing tumor-derived chemotactic factors such as Bv8 and S100A8.<br /><br />The research suggests that 5-FU and S-1 can improve the anti-tumor efficacy of ICIs by stimulating cell death in tumor cells and reducing immune-suppressive cells in the tumor microenvironment. These findings indicate that fluoropyrimidine could be an immunologically optimal partner for ICI therapies, potentially leading to improved therapeutic outcomes for patients with thoracic malignancies.

Asset Subtitle

Hirokazu Ogino

Meta Tag

Speaker Hirokazu Ogino

Topic Tumor Biology – Translational Biology

Keywords

fluoropyrimidine

5-fluorouracil

S-1

immune checkpoint inhibitors

thoracic malignancies

immunogenic cell death

myeloid-derived suppressor cells

calreticulin

anti-tumor immune response

tumor microenvironment