Clinical Significance of a CD3/CD8-Based Immunoscore in Neuroblastoma Patients Using Digital Pathology

Liang Zeng; Shu-Hua Li; Shuo-Yu Xu; Shuo-Yu Xu; Kai Chen; Liang-Jun Qin; Xiao-Yun Liu; Fang Wang; Sha Fu; Ling Deng; Feng-Hua Wang; Lei Miao; Le Li; Na Liu; Ran Wang; Hai-Yun Wang; Hai-Yun Wang

doi:10.3389/fimmu.2022.878457

Frontiers in Immunology (May 2022)

Clinical Significance of a CD3/CD8-Based Immunoscore in Neuroblastoma Patients Using Digital Pathology

Liang Zeng,
Shu-Hua Li,
Shuo-Yu Xu,
Shuo-Yu Xu,
Kai Chen,
Liang-Jun Qin,
Xiao-Yun Liu,
Fang Wang,
Sha Fu,
Ling Deng,
Feng-Hua Wang,
Lei Miao,
Le Li,
Na Liu,
Ran Wang,
Hai-Yun Wang,
Hai-Yun Wang

Affiliations

Liang Zeng: Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Shu-Hua Li: Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Shuo-Yu Xu: Bio-totem Pte. Ltd., Foshan, China
Shuo-Yu Xu: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
Kai Chen: Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Liang-Jun Qin: Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Xiao-Yun Liu: Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Fang Wang: Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Sha Fu: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Cellular & Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Ling Deng: Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Feng-Hua Wang: Departments of Thoracic Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Lei Miao: Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Le Li: Departments of Thoracic Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Na Liu: Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China
Ran Wang: 0Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Hai-Yun Wang: Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China
Hai-Yun Wang: Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangzhou, China

DOI: https://doi.org/10.3389/fimmu.2022.878457
Journal volume & issue: Vol. 13

Abstract

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BackgroundInfiltrating immune cells have been reported as prognostic markers in many cancer types. We aimed to evaluate the prognostic role of tumor-infiltrating lymphocytes, namely CD3+ T cells, CD8+ cytotoxic T cells and memory T cells (CD45RO+), in neuroblastoma.Patients and MethodsImmunohistochemistry was used to determine the expression of CD3, CD8 and CD45RO in the tumor samples of 244 neuroblastoma patients. We then used digital pathology to calculate the densities of these markers and derived an immunoscore based on such densities.ResultsDensities of CD3+ and CD8+ T cells in tumor were positively associated with the overall survival (OS) and event-free survival (EFS), whereas density of CD45RO+ T cells in tumor was negatively associated with OS but not EFS. An immunoscore with low density of CD3 and CD8 (CD3-CD8-) was indictive of a greater risk of death (hazard ratio 6.39, 95% confidence interval 3.09-13.20) and any event (i.e., relapse at any site, progressive disease, second malignancy, or death) (hazard ratio 4.65, 95% confidence interval 2.73-7.93). Multivariable analysis revealed that the CD3-CD8- immunoscore was an independent prognostic indicator for OS, even after adjusting for other known prognostic indicators.ConclusionsThe new immunoscore based on digital pathology evaluated densities of tumor-infiltrating CD3+ and CD8+ T cells contributes to the prediction of prognosis in neuroblastoma patients.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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