Anti-CD4 treatment-induced IL18Rahi CD8+ T cells show highly effector profile

Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, enriches IL18Rahi CD8+ T cells that elicit robust anti-tumor immunity in B16F10 melanoma. To investigate gene-expression profile of IL18Rahi subset, we conducted transcriptome analysis. Overall design: The model of mouse melanoma (B16F10) was used to study IL18Rahi CD8+ T cells. We designed a regimen that utilizes cyclophosphamide treatment, adoptive transfer of tumor-specific T cells, and anti-CD4 treatment, a combination that synergistically increases the efficacy of adoptive T cell therapy. Three days after the B16F10 challenge, C57BL/6 mice sequentially received cyclophosphamide, ex vivo-primed Pmel-1 cells (melanoma-specific TCR-transgenic CD8+ T cells), and IL-2. A transient treatment (on day 10, 17, and 24) of anti-CD4 started seven days after cyclophosphamide treatment. Twenty-five days after the tumor challenge, cells from lymphoid tissues of the mice were magnetically isolated based on the IL18Ra expression and subjected to transcriptome analysis.