title: Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma.
abstract: We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, and we performed studies to test the hypothesis that clinical patterns and immune infiltrates differ at progression on these treatments. We observed rapid clinical progression kinetics in patients on targeted therapy compared to immune checkpoint blockade. To gain insight into possible immune mechanisms behind these differences, we performed deep immune profiling in tumors of patients on therapy. We demonstrated low CD8+T-cell infiltrate on targeted therapy and high CD8+T-cell infiltrate on immune checkpoint blockade at clinical progression. These data have important implications, and suggest that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma.
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Cooper
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reuben
authors.affiliation: Genomic Medicine, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Spencer
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Prieto
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Austin-Breneman
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Cara
authors.initials: C
authors.lastname: Haymaker
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Vancheswaran
authors.initials: V
authors.lastname: Gopalakrishnan
authors.affiliation: Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.affiliation: Division of Medical Oncology, Massachusetts General Hospital , Boston, MA, USA.
authors.forename: Dennie T
authors.initials: DT
authors.lastname: Frederick
authors.affiliation: Division of Medical Oncology, Massachusetts General Hospital , Boston, MA, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Rodabe N
authors.initials: RN
authors.lastname: Amaria
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Glitza
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Adi
authors.initials: A
authors.lastname: Diab
authors.affiliation: Immunology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vence
authors.affiliation: Translational Molecular Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.affiliation: Translational Molecular Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Parra
authors.affiliation: Translational Molecular Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Department of Cell, Developmental and Cancer Biology and Knight Cancer Institute, Oregon Health and Science University , Portland, OR, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA, USA.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Division of Medical Oncology, Massachusetts General Hospital , Boston, MA, USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.affiliation: Genomic Medicine, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.affiliation: Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Stem Cell Transplantation, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Clise-Dwyer
authors.affiliation: Immunology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.affiliation: Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wargo
keywords: BRAF; CTLA-4; Immune checkpoint blockade; PD-1; melanoma; targeted therapy