Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Whijae Roh; Pei-Ling Chen; Alexandre Reuben; Christine N. Spencer; Peter A. Prieto; John P. Miller; Vancheswaran Gopalakrishnan; Feng Wang; Zachary A. Cooper; Sangeetha M. Reddy; Curtis Gumbs; Latasha Little; Qing Chang; Wei-Shen Chen; Khalida Wani; Mariana Petaccia De Macedo; Eveline Chen; Jacob L. Austin-Breneman; Hong Jiang; Jason Roszik; Michael T. Tetzlaff; Michael A. Davies; Jeffrey E. Gershenwald; Hussein Tawbi; Alexander J. Lazar; Patrick Hwu; Wen-Jen Hwu; Adi Diab; Isabella C. Glitza; Sapna P. Patel; Scott E. Woodman; Rodabe N. Amaria; Victor G. Prieto; Jianhua Hu; Padmanee Sharma; James P. Allison; Lynda Chin; Jianhua Zhang; Jennifer A. Wargo; P. Andrew Futreal

doi:10.1126/scitranslmed.aah3560

Research ArticleCancer

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Whijae Roh¹,²,*,
Pei-Ling Chen¹,³,*,
Alexandre Reuben⁴,*,
Christine N. Spencer¹,
Peter A. Prieto⁴,
John P. Miller⁵,
Vancheswaran Gopalakrishnan⁴,
Feng Wang¹,
Zachary A. Cooper¹,⁴,
Sangeetha M. Reddy⁶,
Curtis Gumbs¹,
Latasha Little¹,
Qing Chang¹,
Wei-Shen Chen¹,³,
Khalida Wani⁷,
Mariana Petaccia De Macedo⁷,⁸,
Eveline Chen⁷,
Jacob L. Austin-Breneman⁴,
Hong Jiang⁴,
Jason Roszik¹,⁹,
Michael T. Tetzlaff³,
Michael A. Davies⁹,
Jeffrey E. Gershenwald⁴,
Hussein Tawbi⁹,
Alexander J. Lazar⁴,⁷,
Patrick Hwu⁹,
Wen-Jen Hwu⁹,
Adi Diab⁹,
Isabella C. Glitza⁹,
Sapna P. Patel⁹,
Scott E. Woodman⁹,
Rodabe N. Amaria⁹,
Victor G. Prieto³,
Jianhua Hu¹⁰,
Padmanee Sharma¹¹,¹²,
James P. Allison¹¹,
Lynda Chin¹³,
Jianhua Zhang¹⁴,
Jennifer A. Wargo¹,⁴,†,‡ and
P. Andrew Futreal¹,†,‡

¹Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²Cancer Biology Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
³Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁴Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁵Oncology Research for Biologics and Immunotherapy Translation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁷Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸Pathology Department, A.C.Camargo Cancer Center, São Paulo, SP-01509-010, Brazil.
⁹Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁰Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹¹Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹²Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹³University of Texas System, Austin, TX 78701, USA.
¹⁴Applied Cancer Science Institute, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

↵‡Corresponding author. Email: afutreal{at}mdanderson.org (P.A.F.); jwargo{at}mdanderson.org (J.A.W.)

↵* These authors contributed equally to this work.
↵† Co-senior authors.

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Science Translational Medicine 01 Mar 2017:
Vol. 9, Issue 379, eaah3560
DOI: 10.1126/scitranslmed.aah3560

Whijae Roh

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Cancer Biology Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.

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Pei-Ling Chen

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Alexandre Reuben

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Christine N. Spencer

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Peter A. Prieto

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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John P. Miller

Oncology Research for Biologics and Immunotherapy Translation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Vancheswaran Gopalakrishnan

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Feng Wang

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Zachary A. Cooper

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Sangeetha M. Reddy

Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Curtis Gumbs

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Latasha Little

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Qing Chang

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Wei-Shen Chen

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Khalida Wani

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Mariana Petaccia De Macedo

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Pathology Department, A.C.Camargo Cancer Center, São Paulo, SP-01509-010, Brazil.

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Eveline Chen

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jacob L. Austin-Breneman

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Hong Jiang

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jason Roszik

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Michael T. Tetzlaff

Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Michael A. Davies