In carcinogenesis, the tumor cell microenvironment engendered by tumor cells profits from unceasing interaction of tumor-infiltrating immune cells to tumor-derived factors, thus modifying immune cell responses and directly or indirectly participating to cancer cell expansion, tumor growth, and progression. Immune escape mechanisms are in place and those appear to involve the enrolment of regulatory cells including regulatory T cells (Tregs) and regulatory B cells (Bregs). Documentation of immune suppressive developments and cell-to-cell direct or indirect interactions in tumor microenvironment has emerged and therapeutic approaches targeting various cell-mediated regulatory mechanisms have been established. This chapter discusses major accomplishments in the field, focusing on Bregs and their role in carcinogenesis, regulation of antitumor immunity, and their implication in tumor immunotherapeutic approaches.