Neuroendocrine system plays a critical role in regulating the immune system, and therefore the progression and prognosis of pancreatic neuroendocrine tumors (pNETs) may be largely influenced and reflected by immune cell levels. Lymphocytes are crucial immune cells that correlate with tumorigenesis and tumor progression, and lymphocyte subsets in peripheral blood, which include CD4+ and CD8+ T cells, B cells and NK cells, are reported to reflect tumor prognosis and progression in various cancer types. We thus speculated that peripheral lymphocyte subset proportion may reflect the state of progression and predict tumor prognosis of pNETs.
A retrospective, follow-up cohort study consisting 73 patients diagnosed as pNETs was conducted. Flow cytometry was performed to analyze peripheral lymphocyte subsets. Ultivariate analyses were performed using the stepwise Cox hazards model, and Kaplane-Meier methods and log-rank tests were used for the comparison of survival rates, Mann-Whitney U test were used for analyses of the correlation between lymphocyte subset percentage and clinicopathologic parameters.
pNET patients with distant metastasis were associated with lower CD3+ T cell (p = 0.003), lower CD4+ T cell (p = 0.006) and higher NK cell (p = 0.003) percentage in peripheral blood. Lower percentage of CD3+, CD4+ T cells, B cells and higher percentage of NK cells in peripheral blood were associated with shorter progression-free survival (PFS). Distant metastasis (HR = 29.194, 95%CI: 6.865 to 124.144 p < 0.001) and lower percentage peripheral B cells turned out to be independent risk factors for PFS both in all patient group (HR = 12.232 95%CI: 2.883 to 51.907, p = 0.001) and in group of patients without distant metastasis (HR = 6.744, 95%CI: 1.257 to 36.172, p = 0.026).
CD3+, CD4+ T cell and NK cell percentage in peripheral blood may reflect the the status of distant metastasis in pNET patients. The percentage of peripheral B cells cells may independently predict the progression of pNET patients with or without distant metastasis, making them promising clinical indicators to instruct the frequency for reexaminations after primary medical treatment.
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