Investigation of CD4 T cell help and MHC II in therapeutic vaccinations against liver cancer

The role of CD4 T cells in tumor immunity is not completely understood, as CD4 T cells recognize MHC class II epitopes expressed on antigen-presenting cells but not on tumor cells. Nevertheless, they send critical signals to dendritic cells, which then upregulate the expression of MHC class I molecules, costimulatory molecules, and secretion of cytokines. The overall goal of our study is to determine the importance of CD4 T cells in adaptive immune responses and immunotherapy against HCC.

Mice underwent implantation with HCC cells with different expression of MHC class II epitopes, the resulting tumor growth kinetics, overall survival and specific CD8 and CD4 T cell immune responses in peripheral blood were analyzed by flow cytometry. Using heterologous T cell vaccination (DC-CoAT) that allows for rapid and strong T cell responses, we generated CD8 T cell responses specific for the MHC class I neoantigen Adpgkmut, as well as CD4 T cell responses specific for the MHC class II neoantigen Itgb1mut. Boosters were performed with or without concurrent administration of the MHC class II epitope Itgb1mut.

Treated mice showed a high tumor specific immune response for both CD8 and CD4 T cells. Furthermore, their survival was prolonged with partially tumor regress. In treated mice that were inoculated with an HCC cell line containing the MHC class II transactivator CIITA, the tumors even regressed completely. To better understand the mechanisms of CD4 T cell help, future experiments will characterize the composition of tumor-infiltrating cells by histology and spectral flow cytometry.

Publication History

Article published online:
20 January 2025