title: TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination.
abstract: Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Hsu
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Shaina
authors.initials: S
authors.lastname: Sedighim
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Department of Medicine (Hematology/Oncology), David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|The Medical Scientist Training Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Antonios
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Everson
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tucker
authors.affiliation: Department of Biostatistics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Emerson
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Yusko
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sanders
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Yong
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Tom B
authors.initials: TB
authors.lastname: Davidson
authors.affiliation: Department of Biostatistics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liau
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Prins
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000637:transplantation*; D018450:Disease Progression; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000378:metabolism*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods
chemical_list: D011948:Receptors, Antigen, T-Cell