Preclinical work in murine models suggests that local
radiotherapy plus intratumoral syngeneic dendritic cells (DC) injection can mediate immunologic
tumor eradication.
Radiotherapy affects the immune response to
cancer, besides the direct impact on the
tumor cells, and other ways to coordinate immune modulation with
radiotherapy have been explored. We review here the potential for immune-mediated anticancer activity of radiation on
tumors. This can be mediated by differential
antigen acquisition and presentation by DC, through changes of lymphocytes' activation, and changes of
tumor susceptibility to immune clearance. Recent work has implemented the combination of external beam
radiation therapy (EBRT) with intratumoral injection of DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with
radiation therapy with five HLA-A2(+) subjects with high-risk, localized
prostate cancer; the protocol used
androgen suppression, EBRT (25 fractions, 45 Gy), DC
injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant apoptosis-inducing EBRT plus intra-tumoral DC in
soft tissue sarcoma, to test if this would increase immune activity toward
soft tissue sarcoma associated
antigens. In the future,
radiation therapy approaches designed to optimize immune stimulation at the level of DC, lymphocytes,
tumor and stroma effects could be evaluated specifically in clinical trials.