Is the Induction of Tumor Cell Senescence the Key to a Good Irradiated Tumor Vaccine?

Abstract

Along with surgery and chemotherapy, radiation therapy (RT) is a mainstay of both curative and palliative anticancer treatment. Recent US Food and Drug Administration approval of two immunotherapeutic agents brings immunotherapy into this clinical armamentarium. There is strong emerging rationale for a clinical partnership between RT and immunotherapy in cancer treatment, based primarily on advances in our understanding of the molecular basis of the activation of the innate immune system. In this context, in this issue of Molecular Therapy, Meng et al. present work that further refines our understanding of the immunological mechanisms underlying the systemic effects of RT.1 The new work shows that RT-induced senescence is the key event driving antitumor immunity in their model system. The report corroborates other studies in preclinical animal models that demonstrate that ionizing radiation (IR) markedly alters the tumor microenvironment.2,3 IR increases tumor cell immunogenicity by improving antigen processing and presentation as well as by engendering immunogenic tumor cell death, which, together with the production of intratumoral proinflammatory cytokines and chemokines, links innate immune system activation to the development of a broadening adaptive cellular immune response that is directed toward tumor cells outside the radiation field.2,3,4