title: Immune Modulation by Androgen Deprivation and Radiation Therapy: Implications for Prostate Cancer Immunotherapy.
abstract: Prostate cancer patients often receive androgen deprivation therapy (ADT) in combination with radiation therapy (RT). Recent evidence suggests that both ADT and RT have immune modulatory properties. First, ADT can cause inﬁltration of lymphocytes into the prostate, although it remains unclear whether the inﬂux of lymphocytes is beneﬁcial, particularly with the advent of new classes of androgen blockers. Second, in rare cases, radiation can elicit immune responses that mediate regression of metastatic lesions lying outside the ﬁeld of radiation, a phenomenon known as the abscopal response. In light of these ﬁndings, there is emerging interest in exploiting any potential synergy between ADT, RT, and immunotherapy. Here, we provide a comprehensive review of the rationale behind combining immunotherapy with ADT and RT for the treatment of prostate cancer, including an examination of the current clinical trials that employ this combination. The reported outcomes of several trials demonstrate the promise of this combination strategy; however, further scrutiny is needed to elucidate how these standard therapies interact with immune modulators. In addition, we discuss the importance of synchronizing immune modulation relative to ADT and RT, and provide insight into elements that may impact the ability to achieve maximum synergy between these treatments.
authors.affiliation: Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC V8R 6V5, Canada. Jennifer.Kalina@bccancer.bc.ca.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kalina
authors.affiliation: Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC V8R 6V5, Canada. dneilson@bccrc.ca.|Department of Biochemistry & Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada. dneilson@bccrc.ca.
authors.forename: David S
authors.initials: DS
authors.lastname: Neilson
authors.affiliation: Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC V8R 6V5, Canada. acomber@bccrc.ca.|Department of Biochemistry & Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada. acomber@bccrc.ca.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Comber
authors.affiliation: British Columbia Cancer Agency, Victoria, BC, V8R 6V5, Canada. Jennifer.Rauw@bccancer.bc.ca.|Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Jennifer.Rauw@bccancer.bc.ca.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rauw
authors.affiliation: British Columbia Cancer Agency, Victoria, BC, V8R 6V5, Canada. AAlexander3@bccancer.bc.ca.|Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. AAlexander3@bccancer.bc.ca.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Alexander
authors.affiliation: British Columbia Cancer Agency, Victoria, BC, V8R 6V5, Canada. JVergidis@bccancer.bc.ca.|Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. JVergidis@bccancer.bc.ca.
authors.forename: Joanna
authors.initials: J
authors.lastname: Vergidis
authors.affiliation: Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC V8R 6V5, Canada. jjlum@bccancer.bc.ca.|Department of Biochemistry & Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada. jjlum@bccancer.bc.ca.
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Lum
keywords: androgen deprivation therapy; cancer vaccines; checkpoint inhibitors; immunotherapy; prostate cancer; radiation therapy