Compared with B-cell lymphomas with low IFN signaling (left), high tumor IFN signaling (right) is associated with a higher number of tumor-associated macrophages, a higher level of systemic inflammatory molecules, and increased expression of immune checkpoint ligands, such as PD-L1 and MHC class II on tumor cells, which could inhibit T cells via PD-1 and LAG-3, respectively. Both high tumor IFN signaling in the tumor microenvironment and high levels of monocytic MDSCs in the circulation are associated with lower CAR T-cell expansion and a lower rate of durable responses.