Pegylated recombinant human granulocyte colony-stimulating factor regulates the immune status of patients with small cell lung cancer

Abstract

Background: Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG-rhG-CSF influences immune cells, such as lymphocytes, remains unclear.

Methods: A total of 17 treatment-naïve SCLC patients were prospectively enrolled and divided into the PEG-rhG-CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4-6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3⁺ T, CD4⁺ T, CD8⁺ T, NK, and B cells. The diversity and clonality of the T-cell receptor (TCR) repertoire was analyzed by next-generation sequencing.

Results: In the PEG-rhG-CSF group, the proportions of CD3⁺ T and CD4⁺ T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8⁺ T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG-rhG-CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG-rhG-CSF group. The change in TCR diversity was significantly correlated with changes in the CD3⁺ T or CD4⁺ T cell proportions, but not the CD8⁺ T cell proportion.

Conclusions: PEG-rhG-CSF regulates the immune status of SCLC patients; CD4⁺ T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC.

Key points: PEG-rhG-CSF regulates SCLC immunity. PEG-rhG-CSF increased CD3⁺ T and CD4⁺ T cell proportions. PEG-rhG-CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3⁺ T or CD4⁺ T changes.

Keywords: T-cell receptor; immune status; lymphocyte subsets; pegylated recombinant human granulocyte colony-stimulating factor; small cell lung cancer.