Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.
Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.
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DOI：
10.1371/journal.pone.0085398
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Oppenheim JJ
中科院分区：
文献类型：
--
作者：
Chen X;Yang Y;Zhou Q;Weiss JM;Howard OZ;McPherson JM;Wakefield LM;Oppenheim JJ
TGFβ is reportedly responsible for accumulation of CD4+Foxp3+ regulatory T cells (Tregs) in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3) antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b+Gr1+ cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination.
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DOI：
10.1016/j.clim.2013.08.007
发表时间：
2013-12
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Horwitz DA;Pan S;Ou JN;Wang J;Chen M;Gray JD;Zheng SG
通讯作者：
Zheng SG
影响因子：
11.2
作者：
Le DT;Jaffee EM
通讯作者：
Jaffee EM
DOI：
10.1084/jem.20030152
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Hardegen N;Lei KJ;Li L;Marinos N;McGrady G;Wahl SM
通讯作者：
Wahl SM
影响因子：
--
作者：
Pulaski, B A;Ostrand-Rosenberg, S
通讯作者：
Ostrand-Rosenberg, S
影响因子：
11.2
作者：
Moschella, Federica;Valentini, Mara;Proietti, Enrico
通讯作者：
Proietti, Enrico