期刊
CANCER CELL INTERNATIONAL
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12935-021-01838-7
关键词
GM-CSF; CHOP; R-CHOP; Diffuse large B-cell lymphoma; Tumor microenvironment; Macrophage
类别
资金
- Zhejiang Provincial Natural Science Foundation [LY19H270004, LY15H29004]
- Special project for the modernization of traditional Chinese medicine in zhejiang province [2020ZX007]
- National TCM clinical research base construction project [2015H0105]
- Zhejiang Traditional Medicine and Technology Program for Young Scholar [2021ZQ030]
The study shows that CHOP and R-CHOP treatments potentiate the anti-tumor properties of macrophages by suppressing AKT signaling, with GM-CSF further enhancing their effects.
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.
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