UM
Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide on a mouse model of breast cancer
Xin Chen1,3; Yuan Yang2; Qiong Zhou3; Jonathan M. Weiss4; OlaMae Zack Howard3; John M. McPherson5; Lalage M. Wakefield2; Joost J. Oppenheim3
2014-01
Source PublicationPLOS ONE
ISSN1932-6203
Volume9Issue:1
Abstract

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.

DOIhttp://doi.org/10.1371/journal.pone.0085398
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000329866300075
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorXin Chen; Joost J. Oppenheim
Affiliation1.Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, United States of America
2.Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America
3.Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America
4.4 Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America
5.Genzyme Corporation, Framingham, Massachusetts, United States of America
Recommended Citation
GB/T 7714
Xin Chen,Yuan Yang,Qiong Zhou,et al. Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide on a mouse model of breast cancer[J]. PLOS ONE,2014,9(1).
APA Xin Chen.,Yuan Yang.,Qiong Zhou.,Jonathan M. Weiss.,OlaMae Zack Howard.,...&Joost J. Oppenheim.(2014).Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide on a mouse model of breast cancer.PLOS ONE,9(1).
MLA Xin Chen,et al."Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide on a mouse model of breast cancer".PLOS ONE 9.1(2014).
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