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

View ORCID ProfileWhijae Roh¹,²,*,
View ORCID ProfilePei-Ling Chen¹,³,*,
View ORCID ProfileAlexandre Reuben⁴,*,
View ORCID ProfileChristine N. Spencer¹,
Peter A. Prieto⁴,
View ORCID ProfileJohn P. Miller⁵,
View ORCID ProfileVancheswaran Gopalakrishnan⁴,
Feng Wang¹,
View ORCID ProfileZachary A. Cooper¹,⁴,
Sangeetha M. Reddy⁶,
View ORCID ProfileCurtis Gumbs¹,
View ORCID ProfileLatasha Little¹,
Qing Chang¹,
View ORCID ProfileWei-Shen Chen¹,³,
Khalida Wani⁷,
Mariana Petaccia De Macedo⁷,⁸,
View ORCID ProfileEveline Chen⁷,
View ORCID ProfileJacob L. Austin-Breneman⁴,
Hong Jiang⁴,
View ORCID ProfileJason Roszik¹,⁹,
View ORCID ProfileMichael T. Tetzlaff³,
Michael A. Davies⁹,
View ORCID ProfileJeffrey E. Gershenwald⁴,
View ORCID ProfileHussein Tawbi⁹,
View ORCID ProfileAlexander J. Lazar⁴,⁷,
View ORCID ProfilePatrick Hwu⁹,
View ORCID ProfileWen-Jen Hwu⁹,
View ORCID ProfileAdi Diab⁹,
View ORCID ProfileIsabella C. Glitza⁹,
Sapna P. Patel⁹,
Scott E. Woodman⁹,
Rodabe N. Amaria⁹,
View ORCID ProfileVictor G. Prieto³,
Jianhua Hu¹⁰,
Padmanee Sharma¹¹,¹²,
James P. Allison¹¹,
Lynda Chin¹³,
Jianhua Zhang¹⁴,
View ORCID ProfileJennifer A. Wargo¹,⁴,†,‡ and
View ORCID ProfileP. 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

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.

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Pei-Ling Chen

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Alexandre Reuben

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Christine N. Spencer

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Peter A. Prieto

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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John P. Miller

5Oncology Research for Biologics and Immunotherapy Translation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Vancheswaran Gopalakrishnan

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Feng Wang

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Zachary A. Cooper

1Department of Genomic Medicine, 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.

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Sangeetha M. Reddy

6Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Curtis Gumbs

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Latasha Little

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Qing Chang

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Wei-Shen Chen

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Khalida Wani

7Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Mariana Petaccia De Macedo

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.

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Eveline Chen

7Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jacob L. Austin-Breneman

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Hong Jiang

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jason Roszik

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Michael T. Tetzlaff

3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Michael A. Davies

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jeffrey E. Gershenwald

4Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Hussein Tawbi

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Alexander J. Lazar

4Department of Surgical Oncology, 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.

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Patrick Hwu

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Wen-Jen Hwu

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Adi Diab

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Isabella C. Glitza

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Sapna P. Patel

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Scott E. Woodman

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Rodabe N. Amaria

9Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Victor G. Prieto

3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jianhua Hu

10Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Padmanee Sharma

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.

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James P. Allison

11Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Lynda Chin

13University of Texas System, Austin, TX 78701, USA.

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Jianhua Zhang

14Applied Cancer Science Institute, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Jennifer A. Wargo

1Department of Genomic Medicine, 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.

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For correspondence: afutreal@mdanderson.org jwargo@mdanderson.org

P. Andrew Futreal

1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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For correspondence: afutreal@mdanderson.org jwargo@mdanderson.org

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

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