The liver as a cytokine factory working on mRNA blueprints for cancer immunotherapy

mRNA has the potential to encode both vaccines and immunomodulatory proteins for cancer immunotherapy. In this issue, Beck et al. report on lipopolyplexed mRNAs encoding albumin-stabilized interleukin-2 to transduce liver cells. These mRNAs attain antitumor efficacy on subcutaneous mouse tumors even if malignant cells lack major histocompatibility complex class I (MHC class I) expression. mRNA has the potential to encode both vaccines and immunomodulatory proteins for cancer immunotherapy. In this issue, Beck et al. report on lipopolyplexed mRNAs encoding albumin-stabilized interleukin-2 to transduce liver cells. These mRNAs attain antitumor efficacy on subcutaneous mouse tumors even if malignant cells lack major histocompatibility complex class I (MHC class I) expression. Long-lasting mRNA-encoded interleukin-2 restores CD8+ T cell neoantigen immunity in MHC class I-deficient cancersBeck et al.Cancer CellMarch 14, 2024In BriefMHC-I antigen presentation deficiency is a common cancer immune escape mechanism. Beck et al. show that combining tumor-targeting antibodies with IL-2 mRNA induces rejection of MHC class I-deficient tumors otherwise resistant to immune-, chemo-, and radiotherapy. Unexpectedly, efficacy is dependent on a crosstalk between CD8+ T cells and macrophages. Full-Text PDF