Methylation cytometric pretreatment blood immune profiles with tumor mutation burden as prognostic indicators for survival outcomes in head and neck cancer patients on anti-PD-1 therapy

Ze Zhang; Kartik Sehgal; Keisuke Shirai; Rondi A Butler; John K Wiencke; Devin C Koestler; Geat Ramush; Min Kyung Lee; Annette M Molinaro; Hannah G Stolrow; Ariel Birnbaum; Lucas A Salas; Robert I Haddad; Karl T Kelsey; Brock C Christensen

doi:10.1038/s41698-024-00759-8

Methylation cytometric pretreatment blood immune profiles with tumor mutation burden as prognostic indicators for survival outcomes in head and neck cancer patients on anti-PD-1 therapy

NPJ Precis Oncol. 2024 Nov 18;8(1):267. doi: 10.1038/s41698-024-00759-8.

Authors

Ze Zhang^#^{1

2}, Kartik Sehgal^#^{3

4

5}, Keisuke Shirai⁶, Rondi A Butler^{7

8}, John K Wiencke^{9

10}, Devin C Koestler¹¹, Geat Ramush^{7

8}, Min Kyung Lee^{12

6

13}, Annette M Molinaro⁹, Hannah G Stolrow^{12

6}, Ariel Birnbaum¹⁴, Lucas A Salas^{12

6

13}, Robert I Haddad^{3

4

5}, Karl T Kelsey^{7

8}, Brock C Christensen^{12

6

13}

Affiliations

¹ Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. ze.zhang.gr@dartmouth.edu.
² Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. ze.zhang.gr@dartmouth.edu.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Harvard Medical School, Boston, MA, USA.
⁶ Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
⁷ Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.
⁸ Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
¹¹ Department of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, KS, USA.
¹² Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
¹³ Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
¹⁴ Department of Medicine, Rhode Island Hospital, Providence, RI, USA.

^# Contributed equally.

Abstract

Tissue biomarkers for immune checkpoint inhibitor (ICI) response are limited by tumor sample heterogeneity and availability. This study identifies clinically actionable pretreatment blood biomarkers that are associated with ICI treatment response and survival in recurrent/metastatic head and neck squamous cell carcinoma. A prospective multi-center study enrolled 100 patients before standard-of-care immunotherapy. Blood immune profiles, measured by methylation cytometry, were assessed alongside tumor mutational burden (TMB) and PD-L1 combined proportion score (CPS). TMB and PD-L1 CPS were available for 56 and 91 patients, respectively. High neutrophils, monocytes, and neutrophil-to-lymphocyte ratio were associated with worse survival, while high CD4T cells, especially naïve CD4T cells, and lymphocyte-to-monocyte ratio were associated with better survival. Significant interactions between TMB and peripheral immune profiles for both progression-free and overall survival were found. Clinically relevant pretreatment peripheral immune biomarkers were identified, demonstrating the potential of DNA-based immune profiling to predict ICI response before treatment.

Abstract

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