GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization

Cancer Cell International

Yu Zhang¹  Jingjing Xiang¹  Xianfu Sheng¹  Ni Zhu¹  Jianping Shen¹  Shu Deng¹  Junfa Chen¹  Lihong Yu²  Yan Zhou²  Chenjun Lin² 

[1] Department of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, 310006, Hangzhou, China;First Medical College of Zhejiang Chinese Medical University, Hangzhou, China;

关键词: GM-CSF;    CHOP;    R-CHOP;    Diffuse large B-cell lymphoma;    Tumor microenvironment;    Macrophage;   

DOI  :  10.1186/s12935-021-01838-7

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY