title: Clinical Response of a Patient to Anti-PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors.
abstract: Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers, and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCT). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient initially diagnosed with melanoma via fine needle aspiration was treated with one dose of antibody to PD-1. A core needle biopsy was subsequently performed to acquire sufficient tissue for molecular analysis, which led to a change in diagnosis to metastatic embryonal carcinoma. The testicular GCT cohort of The Cancer Genome Atlas was analyzed using a T-cell gene signature associated with benefit from immunotherapy. Primary tumors (N = 134) were categorized as high (T-cell-inflamed), medium, or low (non-T-cell-inflamed) by their T-cell signature derived from RNAseq data. Anti-PD-1 induced decreases in serum markers and a 33% reduction in tumor volume. Gene expression revealed a T-cell-inflamed tumor microenvironment in 47% of testicular GCTs, including seminoma (83%) and nonseminoma (17%) tumor subtypes. Expression of alpha-fetoprotein (AFP) RNA correlated with lack of the T-cell signature, with increasing AFP RNA inversely correlating with the inflamed signature and expression of IFNγ-associated genes. These data suggest that GCTs can respond to anti-PD-1 and that gene expression profiling supports investigation of immunotherapy for treatment of GCTs. Cancer Immunol Res; 4(11); 903-9. ©2016 AACR.
authors.affiliation: Northshore University HealthSystem, Evanston, Illinois.
authors.forename: Shalin
authors.initials: S
authors.lastname: Shah
authors.affiliation: Northshore University HealthSystem, Evanston, Illinois.|University of Chicago, Chicago, Illinois.
authors.forename: James E
authors.initials: JE
authors.lastname: Ward
authors.affiliation: University of Chicago, Chicago, Illinois.
authors.forename: Riyue
authors.initials: R
authors.lastname: Bao
authors.affiliation: Northshore University HealthSystem, Evanston, Illinois.|University of Chicago, Chicago, Illinois.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Hall
authors.affiliation: Northshore University HealthSystem, Evanston, Illinois.|University of Chicago, Chicago, Illinois.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Brockstein
authors.affiliation: University of Chicago, Chicago, Illinois. jluke@medicine.bsd.uchicago.edu.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Luke
mesh_terms: D000328:Adult; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001706:Biopsy; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013736:Testicular Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D061026:Programmed Cell Death 1 Receptor; D000509:alpha-Fetoproteins