Mechanisms of resistance to BsAb within the lymphoma microenvironment. Potential mechanisms of resistance to BsAb therapy include (A) tumor cell–intrinsic mechanisms, such as antigen loss and activation of immune-evasive gene expression programs, (B) T-cell intrinsic mechanisms, including activation of regulatory T-cells, downregulation of the T-cell receptor, and development of T-cell exhaustion, and (C) T-cell extrinsic mechanisms, including recruitment of immunosuppressive myeloid and/or stromal cells. CAF, cancer-associated fibroblast; IL-10, interleukin-10; MDSC, myeloid-derived suppressor cell; PD-1, programmed death 1; PD-L1, programmed death ligand 1; TAM, tumor-associated macrophage; Teff, effector T cell; Texh, exhausted T cell; TGF-b, transforming growth factor beta; Tim-3, T-cell immunoglobulin mucin-3; Treg, regulatory T cell.