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

David Hsiehchen; Andrew Elliott; Joanne Xiu; Andreas Seeber; Wafik El-Deiry; Emmanuel S Antonarakis; Stephanie L Graff; Michael J Hall; Hossein Borghaei; Dave S B Hoon; Stephen V Liu; Patrick C Ma; Rana R McKay; Trisha Wise-Draper; John Marshall; George W Sledge; David Spetzler; Hao Zhu

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

Cancer Cell. 2024 Dec 9;42(12):1985-1987. doi: 10.1016/j.ccell.2024.10.017. Epub 2024 Nov 21.

Authors

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

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.

Publication types

Letter

MeSH terms

B7-H1 Antigen / antagonists & inhibitors
B7-H1 Antigen / genetics
B7-H1 Antigen / immunology
Humans
Immune Checkpoint Inhibitors* / pharmacology
Immune Checkpoint Inhibitors* / therapeutic use
Immunotherapy / methods
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating / immunology
Mutation*
Neoplasms* / drug therapy
Neoplasms* / genetics
Neoplasms* / immunology
Neoplasms* / therapy
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Programmed Cell Death 1 Receptor* / immunology

Substances

Programmed Cell Death 1 Receptor
Immune Checkpoint Inhibitors
PDCD1 protein, human
B7-H1 Antigen