Spatially defined intratumoral immune biomarkers predict recurrent versus second primary tumors in non-small cell lung cancer

Rekha Mudappathi; Alanna Maguire; Eunhee S. Yi; Yanmei Peng; Jennifer M. Kachergus; Andras Khoor; Kexin Tan; Isabella Zaniletti; Jason A. Wampfler; Yanyan Lou; Pedro A. Reck dos Santos; Jonathan D'Cunha; Zhifu Sun; Li Liu; Diane F. Jelinek; Junwen Wang; Henry D. Tazelaar; E. A. Thompson; Ping Yang

doi:10.1093/pcmedi/pbaf001

Precision Clinical Medicine ›› 2025, Vol. 8 ›› Issue (1) :pbaf001 DOI: 10.1093/pcmedi/pbaf001

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Spatially defined intratumoral immune biomarkers predict recurrent versus second primary tumors in non-small cell lung cancer

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¹ Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ 85259, USA

² College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA

³ Department of Cancer Biology, Mayo Clinic, Scottsdale, AZ 85259, USA

⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ 85259, USA

⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA

⁶ Department of Oncology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing 102400, China

⁷ Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA

⁸ Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32224, USA

⁹ Department of integrated Chinese and Western medicine, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha 410013, China

¹⁰ IZ Statistics LLC, Tampa, FL 33647, USA

¹¹ Division of Biostatistics and Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ 85259, USA

¹² Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA

¹³ Department of Oncology, Mayo Clinic, Jacksonville, FL 32224, USA

¹⁴ Department of Cardiothoracic Surgery, Mayo Clinic, Phoenix, AZ 85054, USA

¹⁵ Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL 32224, USA

¹⁶ Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA

¹⁷ Division of Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong 999077, China

*Ping Yang, yang.ping@mayo.edu

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Rekha Mudappathi, Alanna Maguire, Eunhee S. Yi, Yanmei Peng, Jennifer M. Kachergus, Andras Khoor, Kexin Tan, Isabella Zaniletti, Jason A. Wampfler, Yanyan Lou, Pedro A. Reck dos Santos, Jonathan D'Cunha, Zhifu Sun, Li Liu, Diane F. Jelinek, Junwen Wang, Henry D. Tazelaar, E. A. Thompson, Ping Yang. Spatially defined intratumoral immune biomarkers predict recurrent versus second primary tumors in non-small cell lung cancer. Precision Clinical Medicine, 2025, 8(1): pbaf001 DOI:10.1093/pcmedi/pbaf001

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Acknowledgments

This study was supported by the National Cancer Institute (Grants No. R01-80127, Yang and R01-84354, P.Y.) and the National Institutes of Health (Grant No. LM-R01-13438, L.L., J.W., and P.Y.). We thank J. Shi from the Department of Cancer Biology of Mayo Clinic.

Author contributions

Rekha Mudappathi (Formal analysis, Methodology, Visualization, Writing - original draft, Writing - review & editing), Alanna Maguire (Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing), Eunhee S. Yi (Data curation, Investigation, Writing - review & editing), Yanmei Peng (Data curation, Investigation, Writing - review & editing), Jennifer M. Kachergus (Data curation, Investigation, Visualization, Writing - review & editing), Andras Khoor (Data curation, Writing - review & editing), Kexin Tan (Data curation, Investigation, Writing - review & editing), Isabella Zaniletti (Formal analysis, Investigation, Visualization, Writing - review & editing), Jason A. Wampfler (Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing), Yanyan Lou (Data curation, Writing - review & editing), Pedro A. Reck dos Santos (Conceptualization, Writing - review & editing), Jonathan D'Cunha (Conceptualization, Writing - review & editing), Zhifu Sun (Conceptualization, Writing - review & editing), Li Liu (Conceptualization, Writing - review & editing), Diane F. Jelinek (Conceptualization, Writing - review & editing), Junwen Wang (Conceptualization, Methodology, Writing - review & editing), Henry D. Tazelaar (Conceptualization, Data curation, Writing - review & editing), E.A. Thompson (Conceptualization, Data curation, Writing - review & editing), and Ping Yang (Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing).

Supplementary data

Supplementary data is available at PCMEDI Journal online.

Conflict of interest

None declared. In addition, as an Editorial Board Member of Precision Clinical Medicine, the corresponding author Ping Yang was blinded from reviewing and making decision on this manuscript.

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