B cells are a heterogeneous population in immune defense system with multidirectional functions. In cancer patients, B cell infiltrates are associated with a significant increase of overall survival. We have recently developed a GM-CSF and IL-4 derived fusion cytokine named GIFT4, which has the capability to prime naïve B cells into anti-tumor immune effector cells. Herein, we overview current research findings on B cell anti-tumor functions and B cell-based approaches for cancer immunotherapy. We predict that GIFT4- augmented B cells as a potent cellular therapeutic could provide a new approach for cancer immunotherapy.