Modulation of Myeloid Cell Populations An Alternative Approach to Cancer Immunotherapy

Lung cancer remains the leading cause of cancer-related mortality worldwide, accounting for 18% of all cancer-related deaths globally in 2020. The poor prognosis is largely due to the immunosuppressive tumor microenvironment (TME). Although immune checkpoint inhibitors can be used to treat a subset of lung cancer, limited efficacy in 'cold tumors remains a major concern. Therefore, there is a need for effective immunotherapeutic strategies that remodel the TME. This study aimed to evaluate the potential of combining interleukin-37 (IL-37) with a CD40 agonist and to discover novel approaches to targeting myeloid-derived suppressor cells (MDSCs) and dendritic cells in lung cancer. We designed a preclinical study using murine lung cancer models to test whether IL-37 suppresses MDSCs recruitment and function while CD40 agonism enhances dendritic cell activation, antigen presentation, and CD8 T-cell priming. Additional work is required to understand the translational potential of this approach; however, this suggests that modulation of myeloid populations may represent a promising strategy to convert cold tumors into hot tumors and improve responsiveness to checkpoint blockade in lung cancer.