CpG therapeutic efficacy in a murine model of metastatic Lymphangioleiomyomatosis (LAM) is mediated by plasmacytoid dendritic cell and T cell immune responses

Abstract Introduction: LAM is a slow growing, metastasizing neoplasm affecting women of reproductive age, marked by abnormal growth smooth muscle-like cells leading to cystic lung destruction. has hallmarks cancer, like expression immune checkpoint receptors. Effective cancer therapies promote robust T cell responses through activated dendritic (DCs). Anti-cancer strategies, toll receptor (TLR) activation and inhibition could work as therapy. In this study, we examine the effect CpG, TLR9 agonist, on DC in murine LAM. Methods: We used mouse model metastatic determine survival after biweekly intranasal CpG therapy (10μg/ 5μg) with/ without systemic α-PD-1, rapamycin, or α-CD317 ELISA measure cytokine profile flow cytometry quantify populations between CpG-treated untreated lungs. Results: found that treatment enhances median from 32 60 days (p <0.0001). Efficacy facilitated plasmacytoid DCs. pDC depletion mice decreases 52 (p=0.028). lungs also produce more IFN-α (p=0.031). have increased IFN-γ (p= 0.012) IL-12 0.005), cytokines secreted cytotoxic cells. CpG-treatment synergistic with α-PD-1 (p=0.004) can be administered rapamycin adverse effects survival. Conclusions: LAM, mediated dependent This suggests adjuvant immunotherapy, may offer new options for compatible current standard care, rapamycin. The Foundation Research Grant Award