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.

Synthetic pro‐peptide design to enhance the secretion of heterologous proteins by Saccharomyces cerevisiae

“…Human granulocyte colony‐stimulating factor (hG‐CSF) is a hematopoietic cytokine that acts on cells of the neutrophil lineage, causing the proliferation and differentiation of committed precursor cells and the activation of mature neutrophils (Vanz et al, 2008 ). Since hG‐CSF regulates hematopoietic progenitors and reduces oral toxicity from chemotherapy (Gabrilove et al, 1988 ), it is often used in intensive chemotherapy for small‐cell lung cancer (Sun et al, 2020 ; Timmer‐Bonte et al, 2006 ), chemotherapy‐induced febrile neutropenia (Kuderer et al, 2007 ; Sung et al, 2004 ; Whyte et al, 2011 ), and for the treatment of solid tumors and lymphomas (Lyman et al, 2009 ; Pabst et al, 2012 ). hG‐CSF is also used in bone marrow transplantation (Khoury, 2006 ) and the treatment of severe congenital neutropenia (Rosenberg et al, 2006 ).…”

“…Since hG-CSF regulates hematopoietic progenitors and reduces oral toxicity from chemotherapy (Gabrilove et al, 1988), it is often used in intensive chemotherapy for small-cell lung cancer (Sun et al, 2020;Timmer-Bonte et al, 2006), chemotherapy-induced febrile neutropenia (Kuderer et al, 2007;Sung et al, 2004;Whyte et al, 2011), and for the treatment of solid tumors and lymphomas (Lyman et al, 2009;Pabst et al, 2012). hG-CSF is also used in bone marrow transplantation (Khoury, 2006) and the treatment of severe congenital neutropenia (Rosenberg et al, 2006).…”