RT-induced lymphopenia (14% with protons vs. 39% with photons) limits immunotherapy efficacy by depleting CD4 and CD8 T cells, critical for immune checkpoint inhibitors; RT may enhance immunogenicity by inducing tumor antigen release, but the immunosuppressive tumor microenvironment, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), restricts benefits (see Section 5.5 for further details) [36,44]. The gene discussed is CD4; the disease is neoplasm.