Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4+ T cells to T-regulatory cells

Purevdorj B. Olkhanud, Bazarragchaa Damdinsuren, Monica Bodogai, Ronald E. Gress, Ranjan Sen, Katarzyna Wejksza, Enkhzol Malchinkhuu, Robert P. Wersto, Arya Biragyn

Research output: Contribution to journalArticlepeer-review

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 CD69 High) that express constitutively active Stat3 and B7-H1 High 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.

Original languageEnglish (US)
Pages (from-to)3505-3515
Number of pages11
JournalCancer Research
Volume71
Issue number10
DOIs
StatePublished - May 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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