Dynamics of tumor and immune responses during immune ... · Dynamics of tumor and immune responses during immune checkpoint blockade in non-small cell lung cancer Valsamo Anagnostou
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1
Dynamics of tumor and immune responses during immune checkpoint
blockade in non-small cell lung cancer
Valsamo Anagnostou1,2#*, Patrick M. Forde1,2*, James R. White1, Noushin Niknafs1, Carolyn
Hruban1, Jarushka Naidoo1,2, Kristen Marrone1,2, I.K. Ashok Sivakumar1,3,4, Daniel C. Bruhm1,
Samuel Rosner5, Jillian Phallen1, Alessandro Leal1, Vilmos Adleff1, Kellie N. Smith1,2, Tricia R.
Cottrell1,6, Lamia Rhymee1, Doreen N. Palsgrove1, Christine L. Hann1, Benjamin Levy1,
Josephine Feliciano1, Christos Georgiades7, Franco Verde7, Peter Illei1,2,6, Qing Kay Li1,6,
Edward Gabrielson1,6, Malcolm V. Brock8, James M. Isbell9, Jennifer L. Sauter10, Janis
Taube1,2,6, Robert B. Scharpf1, Rachel Karchin1,3, Drew M. Pardoll1,2, Jamie E. Chaft11, Matthew
D. Hellmann11, Julie R. Brahmer1,2 and Victor E. Velculescu1,2,3#
1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine,
Baltimore, MD 21287, USA
2The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of
Medicine, Baltimore, MD 21287, USA
3Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21204, USA.
4Applied Physics Laboratory, Laurel, MD 20723, USA
5Department of Internal Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA
6Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
7Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
8Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
9 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New
York, NY 10065, USA.
10Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
11Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and
Weill Cornell Medical College, New York, NY 10065, USA
* These authors contributed equally to this work. # Corresponding authors
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Valsamo Anagnostou, M.D., Ph.D. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine 1550 Orleans St, Rm 554 Baltimore, MD 21287 Phone: (410) 614-8948 E-mail: [email protected]
Victor Velculescu, M.D., Ph.D. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine 1550 Orleans St, Rm 544 Baltimore, MD 21287 Phone: (410) 955-7033 E-mail: [email protected]
Disclosure of potential conflicts of interest
P.M.F. receives research funding for clinical trials from Bristol-Myers Squibb,
AstraZeneca/MedImmune, Kyowa, Corvus and Novartis and is a consultant/advisory board
member for Abbvie, AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Celgene, EMD
Serono, Inivata, Lilly, Merck, and Novartis. J.W. is a consultant for Personal Genome Diagnostics.
J.N. receives research funding from Merck, AstraZeneca/MedImmune, Kyowa and Calithera and
is a consultant/advisory board member of Bristol-Myers Squibb, AstraZeneca/MedImmune and
Takeda. C.L.H is a consultant/advisory board member for AbbVie, Bristol-Myers Squibb and
Genentech, receives research funding from Merrimack, GlaxoSmithKline, AbbVie, Bristol-Myers
Squibb, and GlaxoSmithKline. J.S. owns Merck, Pfizer, Thermo Fisher Scientific and Chemed
Corporation stock. J.T. is an advisory board member of Bristol-Meyers Squib, Merck, Astra Zeneca
and Amgen and receives research funding from Bristol-Meyers Squib. B.L is a consultant/advisory
board member of AstraZeneca, Celgene, Genentech Rouche, Eli Lilly, and Takeda and receives
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
We thank Dr. Suzanne Topalian and members of our laboratories for helpful discussions and
critical review of the manuscript.
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Major pathologic response (MPR) was defined as ≤10% viable tumor cells at the time of surgical resection (Forde et al., NEJM, 2018). *exome sequencing was not performed; for these cases CLIA-targeted NGS was
performed for clinical purposes ** the baseline tumor was not available for whole exome sequencing, the resection sample was analyzed and used to identify tumor-specific variants in ctDNA. TCR expansion was
assessed at the time of radiographic response. PFS; progression-free survival, OS; overall survival, ND; not detected, N/A; not evaluable,
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127
Published OnlineFirst December 12, 2018.Cancer Res Valsamo Anagnostou, Patrick M Forde, James R White, et al. checkpoint blockade in non-small cell lung cancerDynamics of tumor and immune responses during immune
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on December 12, 2018; DOI: 10.1158/0008-5472.CAN-18-1127