Alterations and Clinical Value of Peripheral Lymphocyte Subsets and Inflammatory Factors in Paragangliomas.

Objectives: Given the pivotal role of immune and inflammatory responses in tumor patients, the present study aimed to explore alterations and the clinical value of peripheral lymphocyte subsets and inflammatory factors in pheochromocytomas/paragangliomas (PPGLs).

Methods: The clinical data of 327 patients, including 102 patients with metastatic PPGLs, were retrospectively analyzed. Peripheral lymphocyte subsets were determined by flow cytometry. Relationships between immune and inflammatory parameters and clinicopathological characteristics were evaluated by intergroup comparisons and correlation analyses. Univariate and multivariate logistic regression analyses were employed to identify metastatic indicators. The corresponding nomogram was constructed and evaluated for discrimination and calibration.

Results: The median age at diagnosis was 45.0 years, and duration of follow-up was 3.0 years. Compared with those in younger patients (< 45.0 years), most lymphocyte subsets were significantly reduced in older patients (≥ 45 years) (P < .05). The count of lymphocytes, CD3+ T cells and CD4+ T cells were negatively correlated with 24-hour urinary epinephrine and plasma metanephrine levels (R = -0.2 ∼ 0.1, P < .05). In addition, patients with lymph node (n = 37) or bone metastases (n = 41) had a lower percentage of CD4+ T cells (P < .05). Multivariate analysis revealed that CD3+ T cell count ≥ 1446.50/μL, CD4+ T cell% < 39.95%, CD8+ T cell% < 24.95%, CD4+/CD8+ T cell ratio < 2.88, B cell% ≥ 8.65%, TNF-alpha < 12.45 pg/mL, IL-8 < 30.50 pg/mL, and platelets ≥ 269.50 × 109/L were significant indicators of metastatic PPGLs. The area under the curve (AUC) of the nomogram was 0.800 (95% CI: 0.736-0.865).

Conclusion: Immunosenescence, characterized by immune dysfunction with aging, was observed in PPGLs. Higher epinephrine and metanephrine levels might impair host immune response. Monitoring changes in peripheral lymphocyte subsets and serum cytokines could indicate patients' conditions, especially the occurrence of metastasis.