Abstract B cells play an important role in antigen presentation and antibody production. However, they appear to exhibit suppressive function inhibiting autoimmune responses in mice. Yet, it remains unknown whether regulatory B cells exist or participate in cancer progression. Here, we demonstrate that a unique B cel subset is induced from resting B cells by cancer cells. These B cells, designated as tumor Bregs (tBregs), are poorly proliferative and express high level of IL-2Rα. The major function of tBregs is to suppress T cell responses, as they efficiently and in dose dependent manner inhibits a proliferation of T cells stimulated with anti-CD3/28 beads. The suppressive activity of tBregs is a cell contact-dependent, but Fas/FasL- and PD1/B7H1-independent, and unlike any other reported regulatory cells, does not require soluble factors such as IL-2, IL-10, TGFβ, IL-27 and IL-35. Importantly, we show for the first time, tBregs induce a conversion of Tregs from non-regulatory CD4+ T cells. Taken together, tBregs are an important and distinct subset of regulatory cells which promote cancer escape and metastasis through direct and indirect (via Tregs) suppression of cellular responses. This work was supported by the Intramural Research Program of the National Institute on Aging, NIH.