Abstract

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown.MethodsIn the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF.ResultsCHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF.ConclusionsOur work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL.Trial registration Not applicable.

Highlights

  • Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells

  • Smaller tumor size was observed in CHOP groups compared to rituximab and CHOP (R-CHOP) groups, implying that the antitumor effect was more obvious in R-CHOP group than that in CHOP

  • These findings indicated the anti-DLBCL effects of CHOP and R-CHOP, which could be further accelerated by the co-administration of granulocyte-macrophage colony-stimulating factor (GM-CSF)

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Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/ doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. Diffuse large B-cell lymphoma (DLBCL) is one type of the Non-Hodgkin lymphomas (NHLs) known as an aggressive malignancy of the mature B cells [1, 2]. Zhang et al Cancer Cell Int (2021) 21:141 prednisone) chemotherapy or the combination rituximab and CHOP (R-CHOP) chemotherapy [3, 4] This approach generally leads to the significant improvement in the overall survival of patients with NHLs. there are still more than 30 % DLBCL patients lacking of sensitivity to CHOP or R-CHOP treatment [5]. The exact mechanisms underlying the therapeutic role of CHOP and the synergistic effect of Rituximab and GMCSF are still elusive

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