Decoy-resistant IL-18 therapy combined with anti-PD-1 induces CD4+ T cell-mediated elimination of murine β2M-deficient lung tumors

Immunophenotyping of UN-SCC680 tumors treated with DR-18 and anti-PD-1 revealed enrichment of activated CD4+ T cells, as well as the promotion of a pro-inflammatory transcriptional program across CD4+ T cell subsets and the enrichment of pro-inflammatory functions in tumor-infiltrating macrophages. Employing cytotoxicity assays with primary lymphocytes, we found that both CD4+ and CD8+ T cells, as well as NK cells, have the capacity to kill UN-SCC680 β2M-KO tumors.

These results begin to reveal the role of CD4+ T cells in the coordination of MHC class I-independent mechanisms of tumor elimination that have the potential to be enhanced with DR-18 combined with anti-PD-1. This work highlights a potential strategy to overcome or avoid resistance caused by impaired MHC class I antigen presentation.