Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Michael N. Kammer, PhD; Hidetoshi Mori, PhD; Dianna J. Rowe, BS; Sheau-Chiann Chen, PhD; Georgii Vasiukov, PhD; Thomas Atwater, MD; Maria Fernanda Senosain, PhD; Sanja Antic, MD; Yong Zou, MS; Heidi Chen, PhD; Tobias Peikert, MD; Steve Deppen, PhD; Eric L. Grogan, MD; Pierre P. Massion, MD; Steve Dubinett, MD; Marc Lenburg, PhD; Alexander Borowsky, MD; Fabien Maldonado, MD

JTO Clinical and Research Reports (Sep 2023)

Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Michael N. Kammer, PhD,
Hidetoshi Mori, PhD,
Dianna J. Rowe, BS,
Sheau-Chiann Chen, PhD,
Georgii Vasiukov, PhD,
Thomas Atwater, MD,
Maria Fernanda Senosain, PhD,
Sanja Antic, MD,
Yong Zou, MS,
Heidi Chen, PhD,
Tobias Peikert, MD,
Steve Deppen, PhD,
Eric L. Grogan, MD,
Pierre P. Massion, MD,
Steve Dubinett, MD,
Marc Lenburg, PhD,
Alexander Borowsky, MD,
Fabien Maldonado, MD

Affiliations

Michael N. Kammer, PhD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee; Corresponding author. Address for correspondence: Michael N. Kammer, PhD, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt Ingram Cancer Center, 638 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37235.
Hidetoshi Mori, PhD: Department of Pathology, University of California, Davis, Davis, California
Dianna J. Rowe, BS: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Sheau-Chiann Chen, PhD: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Georgii Vasiukov, PhD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Thomas Atwater, MD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Maria Fernanda Senosain, PhD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Sanja Antic, MD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Yong Zou, MS: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Heidi Chen, PhD: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Tobias Peikert, MD: Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota
Steve Deppen, PhD: Division of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; VA Tennessee Valley Healthcare System, Nashville, Tennessee
Eric L. Grogan, MD: VA Tennessee Valley Healthcare System, Nashville, Tennessee; VA Tennessee Valley Healthcare System, Nashville, Tennessee
Pierre P. Massion, MD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
Steve Dubinett, MD: David Geffen School of Medicine at The University of California Los Angeles (UCLA), Los Angeles, California
Marc Lenburg, PhD: School of Medicine, Boston University, Boston, Massachusetts
Alexander Borowsky, MD: Department of Pathology, University of California, Davis, Davis, California
Fabien Maldonado, MD: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

Journal volume & issue: Vol. 4, no. 9
p. 100504

Abstract

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Introduction: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. Methods: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. Results: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27–0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15–0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. Conclusions: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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