In a model of colon cancer, a huge influx of tumor‐specific CD8+ T cells (70% in irradiated tumor vs. 19% in non‐irradiated tumor) and loss of MDSC were observed after high‐dose single fraction of 30 Gy – an effect which was dependent upon DC cross‐presentation, secretion of IFN‐γ and CD40 ligand (CD40L)‐expressing CD4+ T cells. The gene discussed is CD4; the disease is neoplasm.