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Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Clinical Response of a Patient to Anti-PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors.
Cancer Immunology Research 2016 November
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.
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