title: Metastatic Melanoma Patient Had a Complete Response with Clonal Expansion after Whole Brain Radiation and PD-1 Blockade.
abstract: We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8+T cells in the blood expanded and the ratio of CD8+:Treg T cells increased. A CD8+T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone. Immunohistochemical analysis confirmed the presence of CD8+T cells and low PD-L1 expression in the brain metastases before immunotherapy initiation. This sequence of therapy may provide an option for melanoma patients with unresponsive brain metastases. Cancer Immunol Res; 5(2); 100-5. ©2017 AACR.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Haymaker
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: DaeWon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marc
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vence
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ann
authors.initials: A
authors.lastname: Phillip
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Natalie
authors.initials: N
authors.lastname: McQuail
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Irina
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Courtney W
authors.initials: CW
authors.lastname: Hudgens
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Creasy
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. adiab@mdanderson.org cbernatchez@mdanderson.org.
authors.forename: Chantale
authors.initials: C
authors.lastname: Bernatchez
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. adiab@mdanderson.org cbernatchez@mdanderson.org.
authors.forename: Adi
authors.initials: A
authors.lastname: Diab
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060965:Clonal Evolution / Q000235:genetics; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000379:methods; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D015415:Biomarkers; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab