CD4+ T cells facilitate the RT-induced abscopal effect by promoting antigen cross-presentation to CD8+ T cells at unirradiated tumor sites - PubMed
3 months ago
- #Immunotherapy
- #Abscopal effect
- #Radiotherapy
- CD4+ T cells enhance the abscopal effect of radiotherapy (RT) by promoting antigen cross-presentation to CD8+ T cells at non-irradiated tumor sites.
- Combination therapy of RT with αPD-1 and αCTLA-4 showed a stronger abscopal response compared to RT with αPD-1 and IL-2c in mouse models.
- The abscopal effect with RT/αPD-1/αCTLA-4 was dependent on both CD8+ and CD4+ T cells, while RT/αPD-1/IL-2c required only CD8+ T cells.
- Enhanced abscopal effect was associated with increased effector function and reduced exhaustion of tumor-specific CD8+ and CD4+ TILs, and elevated CD80+CD86+ DCs in abscopal tumors.
- CD4+ T cells upregulated CD80/CD86 on cDC1s and enhanced cross-presentation, partly via interferon-γ and tumor necrosis factor.
- Adoptively transferred tumor-specific CD8+ T cells localized to unirradiated tumors in αPD-1/αCTLA-4-treated recipients but not in untreated or CD4+ T cell-depleted mice.