Article
PSGL-1 expression on circulating and tumour infiltrating lymphocytes in GBM patients
PSGL-1 auf zirkulierenden und Tumor-infiltrierenden T-Lymphozyten bei Patienten mit Glioblastoma multiforme
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Published: | June 4, 2021 |
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Objective: We showed previously involvement of P-selectin glycoprotein ligand-1 (PSGL-1) in immune modulatory mechanisms of circulating and intra-tumoral macrophages in patients with glioblastoma multiforme (GBM). The aim of the present study was to characterize PSGL-1 expression on circulating and intra-tumoral T cells in GBM patients.
Methods: Surface expression of PSGL-1 and other activation/exhaustion markers was assessed on circulating (CL, n=14) and tumor infiltrating (TIL, n=10) lymphocytes of newly diagnosed GBM patients using flow cytometry. CL of matched healthy persons were used as controls. Arithmetic mean fluorescence intensity was used to determine expression level. CD4+, CD8+ and the subsets of naive, central memory (Tcm), effector memory (Tem) and CD45RA+ effector memory (Temra) T cells were assessed. All GBM patients received dexamethasone (cumulative dose of 70 mg in mean, range from 4 to 120 mg) before taking the blood sample.
Results: PSGL-1 expression was significantly increased on CD4+ naive and Tem CL subsets in patients compared to controls (CD4+ naive: 25.92 vs 25.86, p=0.048; CD4+ Tem: 19.41 vs 16.11, p=0.017). Expression of CD25 on CL was increased on CD4+ (12.37 vs 7.26, p<0,001) and several CD8+ subsets (Tcm: 4.97 vs 2.72, p=0.024; naive: 2.06 vs 1.49, p=0.012; Tem: 2.10 vs 1.42, p=0.021; Temra: 1.21 vs 1.11, p=0.041) in GBM patients compared to controls. PD-1 expression on CD8+ Tem (1.61 vs 1.25, p=0.029) and CD8+ Temra (2.65 vs 1.83, p=0.035) CL was increased compared to controls. No difference of CTLA-4 expression on CL was seen between the groups.
Tumor analysis showed a decrease of PSGL-1 expression on TIL compared to CL in GBM patients both on CD4+ (TIL: 2.47 vs 22.50 on CL, p<0.001) and CD8+ (TIL: 1.88 vs 28.52 on CL, p<0.001) subsets. PD-1 expression was significantly increased on TIL compared to CL on CD4+ (TIL: 7.03 vs 2.08 on CL, p=0.002) and CD8+ (TIL: 5.32 vs 2.04 on CL, p=0.002) populations. TIM-3 expression was increased on CD4+ TIL compared to CD4+ CL (0.51 vs. 0.19, p=0.002).
Conclusion: The decreased PSGL-1 surface expression on TIL in GBM patients is a novel finding in this study. The increased PSGL-1 surface expression on subsets of circulating CD4+ T cells can be a sign of the systemic anti-inflammation in GBM patients. Whether the dexamethasone medication is a confounder needs to be addressed in further studies. PD1 and TIM 3 expression on TIL was as expected in this study.