Prognosis of Macrophage Density in the Absence of Neutrophils in Differentiated Thyroid Cancer

• Published in: The Journal of surgical research Vol. 256; pp. 458 - 467
• Main Authors: Onuma, Amblessed E., Schoenfield, Lynn, Shen, Chengli, Edwards, Charity, Phay, John E., Shirley, Lawrence A., Tsung, Allan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020
• Subjects: Adult; Aged; Aged, 80 and over; Cytokines; Cytokines - blood; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - prevention & control; Neutrophils - immunology; Preoperative Period; Prognosis; Retrospective Studies; Thyroid cancer; Thyroid Gland - immunology; Thyroid Gland - pathology; Thyroid Gland - surgery; Thyroid Neoplasms - blood; Thyroid Neoplasms - immunology; Thyroid Neoplasms - mortality; Thyroid Neoplasms - surgery; Thyroidectomy; Tumor Microenvironment - immunology; Tumor-associated macrophages; Tumor-Associated Macrophages - immunology; Tumor-associated neutrophils; Young Adult; Tumor-associated neutrophils; Thyroid cancer; Cytokines; Tumor-associated macrophages
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2020.07.032

Despite the advances in treatment of differentiated thyroid cancer (DTC), predicting prognosis remains a challenge. Immune cells in the tumor microenvironment may provide an insight to predicting recurrence. Therefore, the objective of this study was to investigate the association of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) with recurrence in DTC and to identify serum cytokines that correlate with the presence of these immune cells in the tumor. Forty-two DTC tissues from our institutional neoplasia repository were stained for immunohistochemistry markers for TAMs and TANs. In addition, cytokine levels were analyzed from these patients from preoperative blood samples. TAM and TAN staining were compared with clinical data and serum cytokine levels. Neither TAM nor TAN scores alone correlated with tumor size, the presence of lymph node metastases, multifocal tumors, lymphovascular or capsular invasion, or the presence of BRAFV600E mutation (all P > 0.05). There was no association with recurrence-free survival (RFS) in TAN density (mean RFS, 169.1 versus 148.1 mo, P = 0.23) or TAM density alone (mean RFS, 121.3 versus 205.2 mo, P = 0.54). However, when scoring from both markers were combined, patients with high TAM density and TAN negative scores had significantly lower RFS (mean RFS, 50.7 versus 187.3 mo, P = 0.04) compared with the remaining cohort. Patients with high TAM/negative TAN tumors had significantly lower serum levels of interleukin 12p70, interleukin 8, tumor necrosis factor alpha, and tumor necrosis factor beta. In DTCs, high density of TAMs in the absence of TANs is associated with worse outcome. Assessment of multiple immune cell types and serum cytokines may predict outcomes in DTC. •Assessment of multiple immune cell types may predict outcomes in thyroid cancer.•High tumor macrophages in low neutrophil density is associated with poor outcome.•Serum cytokine levels may correlate with tumor immune cell composition.•Lower serum levels of IL-12p70, IL8, TNF-α and TNF-β correlated with poor outcome.