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


Infiltrating 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 Methods

Immunohistochemistry 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.



Densities 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.



The 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.


About the Publisher

Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. Field Chief Editor Luigi Daniele Notarangelo is supported by an outstanding board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.


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