CpG-ODN as novel LAM immunotherapy

Lymphangioleiomyomatosis (LAM) is a rare but serious lung disease mostly affecting women of reproductive age. LAM leads to lung damage through the formation of cysts. Recent research showed that LAM suppresses the anti-LAM immune response, but certain treatments, like checkpoint inhibitors, can help. This study explores using a specific immune booster called CpG-ODN, which activates toll-like receptor 9 (TLR9) on immune cells, as a treatment for LAM alongside other therapies like anti-PD1 and rapamycin. The researchers conducted experiments on mice with LAM to see how well CpG-ODN works. They found that giving CpG-ODN through the nose improved survival rates in mice. Interestingly, lower doses of CpG-ODN led to longer survival but resulted in more and larger LAM nodules than higher doses. The treatment also changed the immune response by reducing certain regulatory T cells while increasing helper T cells and cytotoxic T cells, which are important for fighting infections and cancer. This immune response improvement seems to be linked to a type of immune cell called plasmacytoid dendritic cells (pDCs), as when these cells were removed, the positive effects on survival and immune response were reduced. Additionally, CpG-ODN was effective in both early and later stages of the disease and, importantly, synergized with anti-PD1 therapy and rapamycin, the only FDA-approved LAM treatment. The findings suggest that CpG-ODN could be used to enhance survival rates, indicating that toll-like receptors could serve as therapeutic targets for LAM. The research highlights the immune system’s involvement in disease progression and suggests a mechanism through which immune modulation may improve outcomes in LAM. In conclusion, CpG-ODN shows promise as an effective treatment for LAM, especially when used with other therapies.

Read full article

Menu