Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4+ T Cells to T-Regulatory Cells
Copyright policy )Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4+ T Cells to T-Regulatory Cells
Abstract Pulmonary metastasis of breast cancer requires recruitment and expansion of T-regulatory cells (Treg) that promote escape from host protective immune cells. However, it remains unclear precisely how tumors recruit Tregs to support metastatic growth. Here we report the mechanistic involvement of a unique and previously undescribed subset of regulatory B cells. These cells, designated tumor-evoked Bregs (tBreg), phenotypically resemble activated but poorly proliferative mature B2 cells (CD19+ CD25High CD69High) that express constitutively active Stat3 and B7-H1High CD81High CD86High CD62LLow IgMInt. Our studies with the mouse 4T1 model of breast cancer indicate that the primary role of tBregs in lung metastases is to induce TGF-β–dependent conversion of FoxP3+ Tregs from resting CD4+ T cells. In the absence of tBregs, 4T1 tumors cannot metastasize into the lungs efficiently due to poor Treg conversion. Our findings have important clinical implications, as they suggest that tBregs must be controlled to interrupt the initiation of a key cancer-induced immunosuppressive event that is critical to support cancer metastasis. Cancer Res; 71(10); 3505–15. ©2011 AACR.
- National Institutes of Health United States
- National Institute of Health Pakistan
- National Institute on Aging United States
CD4-Positive T-Lymphocytes, B-Lymphocytes, Lung Neoplasms, Breast Neoplasms, Forkhead Transcription Factors, Mice, SCID, T-Lymphocytes, Regulatory, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Mice, Mice, Inbred NOD, Cell Line, Tumor, Animals, Humans, Female, Neoplasm Metastasis, Neoplasm Transplantation
CD4-Positive T-Lymphocytes, B-Lymphocytes, Lung Neoplasms, Breast Neoplasms, Forkhead Transcription Factors, Mice, SCID, T-Lymphocytes, Regulatory, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Mice, Mice, Inbred NOD, Cell Line, Tumor, Animals, Humans, Female, Neoplasm Metastasis, Neoplasm Transplantation
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).519 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 0.1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!