Mutation burden and anti-PD-1 outcomes are not universally associated with immune cell infiltration or lymphoid activation

David Hsiehchen¹, Andrew Elliott², Joanne Xiu², Andreas Seeber³, Wafik El-Deiry⁴, Emmanuel S Antonarakis⁵, Stephanie L Graff⁶, Michael J Hall⁷, Hossein Borghaei⁸, Dave S B Hoon⁹, Stephen V Liu¹⁰, Patrick C Ma¹¹, Rana R McKay¹², Trisha Wise-Draper¹³, John Marshall¹⁴, George W Sledge², David Spetzler², Hao Zhu¹⁵

Affiliations

¹ Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: gbtwnow@gmail.com.
² Caris Life Sciences, Phoenix, AZ, USA.
³ Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, USA.
⁵ Division of Hematology, Oncology and Transplantation, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.
⁶ Lifespan Cancer Institute, Legorreta Cancer Center at Brown University, Providence, RI, USA.
⁷ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁸ Department of Hematology-Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.
⁹ Department of Translational Molecular Medicine, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
¹⁰ Division of Hematology and Oncology, Georgetown University, Washington, DC, USA.
¹¹ Penn State Cancer Institute, Hershey, PA 17033, USA.
¹² Moores Cancer Center, University of California San Diego Health, La Jolla, CA, USA.
¹³ Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Ruesch Center for The Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
¹⁵ Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

PMID: 39577419
DOI: 10.1016/j.ccell.2024.10.017

Mutation burden and anti-PD-1 outcomes are not universally associated with immune cell infiltration or lymphoid activation

David Hsiehchen et al. Cancer Cell. 2024.

. 2024 Dec 9;42(12):1985-1987.

doi: 10.1016/j.ccell.2024.10.017. Epub 2024 Nov 21.

Authors

Affiliations

¹ Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: gbtwnow@gmail.com.
² Caris Life Sciences, Phoenix, AZ, USA.
³ Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, USA.
⁵ Division of Hematology, Oncology and Transplantation, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.
⁶ Lifespan Cancer Institute, Legorreta Cancer Center at Brown University, Providence, RI, USA.
⁷ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁸ Department of Hematology-Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.
⁹ Department of Translational Molecular Medicine, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
¹⁰ Division of Hematology and Oncology, Georgetown University, Washington, DC, USA.
¹¹ Penn State Cancer Institute, Hershey, PA 17033, USA.
¹² Moores Cancer Center, University of California San Diego Health, La Jolla, CA, USA.
¹³ Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Ruesch Center for The Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
¹⁵ Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

PMID: 39577419
DOI: 10.1016/j.ccell.2024.10.017

Abstract

Analysis of 27,810 patients with advanced cancers treated with anti-PD-1/L1 therapies shows that immune gene signatures or immune cell infiltration is not universally associated with mutation burden or long-term survivors after immunotherapies across cancer entities. Thus, immunological stratification of tumors has limited bearing on the immunogenicity of tumors or immunotherapy outcomes.

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Conflict of interest statement

Declaration of interests A.E., J.X., G.W.S., and D.S. are employees of Caris Life Sciences. S.L.G. serves as a paid consultant/advisor to Pfizer, Daiichi Sankyo, Eli Lilly, AstraZeneca, Genentech, SeaGen, Novartis, and Menarini and has stock ownership in HCA Healthcare. E.S.A. serves as a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Bayer, BMS, Amgen, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis, and Eli Lilly; has received research support (to his institution) from Janssen, J&J, Sanofi, BMS, Pfizer, AstraZeneca, Novartis, Curium, Constellation, Celgene, Merck, Bayer, and Clovis; and is the co-inventor of a patented AR-V7 biomarker technology that has been licensed to Qiagen.

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Mutation burden and anti-PD-1 outcomes are not universally associated with immune cell infiltration or lymphoid activation

Affiliations

Mutation burden and anti-PD-1 outcomes are not universally associated with immune cell infiltration or lymphoid activation

Authors

Affiliations

Abstract

Conflict of interest statement

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Full Text Sources

Medical