title: Radiation therapy combined withListeria monocytogenes-based cancer vaccine synergize to enhance tumor control in the B16 melanoma model.
abstract: Conceptually, the immune system may profoundly influence the efficacy of radiation therapy. Compelling evidence has recently emerged revealing the capacity of local radiation therapy (RT) to induce antitumor immune responses and sparked interest in combining RT with immunotherapy to promote tumor-specific immunity. AListeria monocytogenes(Lm)-based cancer vaccine engineered to express tumor-associated antigen has been shown to effectively retard tumor growth by cell-mediated immune mechanisms. We hypothesized that combining RT andLmvaccine will result in synergistic effects that enhance tumor control. Collectively, our data demonstrate that combination therapy significantly delayed B16 melanoma tumor growth by a mechanism partly dependent on CD8+T cells. Radiotherapy andLmvaccine each induce different aspects of antitumor immunity, resulting in an overall increase in intratumoral numbers of activated T cells, antigen-specific CD8+T cells, natural killer (NK) cells and levels of effector molecules, such as interferon γ (IFNγ) and granzyme B. Thus, radiation andLmvaccine combination therapy is a promising new strategy for the treatment of malignant disease, and further understanding of the mechanisms that underlie efficacy is required to optimize the dosage and schedule for administering the two treatments.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY USA.
authors.forename: Joanne Yh
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Aduro BioTech, Inc, Berkeley, CA USA.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Brockstedt
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY USA.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Lord
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
keywords: B16 melanoma; Listeria monocytogenes-based vaccine; anti-tumor immune response; immunotherapy; radiation therapy
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