title: Inducible expression of cancer-testis antigens in human prostate cancer.
abstract: Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589. These CTAs include NY-ESO1, multiple members of the MAGE and SSX families and NY-SAR35. A subset of CTAs is synergistically induced by the combination of 5AZA and LBH589. We developed an ex vivo organ culture using human PC biopsies for ex vivo drug treatments to evaluate these agents in clinical samples. These assays found significant induction of SSX2 in 9/9 distinct patient samples and NY-SAR35 in 7/9 samples. Further, we identify expression of SSX2 in circulating tumor cells (CTC) from patients with advanced PC. These results indicate that epigenetic modifying agents can induce expression of a broad range of neoantigens in human PC and may serve as a useful adjunctive therapy with novel tumor vaccines and checkpoint inhibitors.
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Erika
authors: E
authors: Heninger
authors: University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Timothy E G
authors: TE
authors: Krueger
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Stephanie M
authors: SM
authors: Thiede
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Jamie M
authors: JM
authors: Sperger
authors: University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Brianna L
authors: BL
authors: Byers
authors: University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Madison R
authors: MR
authors: Kircher
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: David
authors: D
authors: Kosoff
authors: Department of Urology, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Bing
authors: B
authors: Yang
authors: Department of Urology, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: David F
authors: DF
authors: Jarrard
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Douglas G
authors: DG
authors: McNeel
authors: Department of Medicine, University of Wisconsin, Madison, Madison, WI 53705, USA.|University of Wisconsin Carbone Cancer Center, Madison, Madison, WI 53705, USA.
authors: Joshua M
authors: JM
authors: Lang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D000077767:Panobinostat; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics; D013737:Testis / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C104948:CTAG1B protein, human; D006877:Hydroxamic Acids; D007211:Indoles; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins; D000077209:Decitabine; D000077767:Panobinostat; D001374:Azacitidine
keywords: cancer testis antigen; epigenetics; methylation; prostate cancer; tumor immunotherapy