Abrahimi et al. evaluate intravesical CAR T cell delivery as a therapeutic platform for organ-confined bladder cancers. By targeting MUC16, they demonstrate intravesical administration uncouples antitumor efficacy from systemic engraftment, overcoming a major CAR T cell toxicity barrier in solid tumors.

Al Jawazneh, Liebold, Leyk et al. show that engulfment of bile acid–loaded hepatic parenchymal cells results in the transfer of bile acids to phagocytic macrophages, altering their inflammatory profile. This identifies dying cells, and specifically their bile acid content, as active modulators of macrophage function, potentially driving chronic inflammation in cholangiopathies such as primary sclerosing cholangitis.

The study by Ongaro et al. identifies IRF8 as a tumor-specific regulator driving CD8⁺ T cell exhaustion: induced by TCR but suppressed by chronic IFN-I, IRF8 promotes TOX and represses effector functions; targeting IRF8/IRF-family network restores anti-tumor immunity, informing immunotherapy strategies for cancer therapy.

Rapid production of the effector cytokine IFN-γ by natural killer (NK) cells is critical for host defense against viral infection. In activated NK cells, IL-12 remodels the RNA polymerase II landscape within minutes, increasing IFN-γ promoter occupancy and pausing in a STAT4- and DDX5-dependent manner.

Harms Pritchard et al. dissect key CD4⁺ T cell/B cell interactions to define signals that govern the development of MBC populations. Surprisingly, IgM⁺ MBCs that form secondary plasmablasts require many of the key programs as IgG⁺ MBCs but do not require GC T follicular helper cells to achieve this state of differentiation.

Depending on the immunization route, location, and antigen dose, BACH2 exerts bidirectional regulation on the differentiation of CXCR5⁻ versus CXCR5⁺ CD4⁺ T cells, orchestrating systemic immunity throughout the body.

Lin et al. identify eIF3e as a translational checkpoint that maintains immune tolerance. Deleting eIF3e in B cells drives pathological B–T cell interactions, lymphoproliferative disease, and lymphoma, highlighting translational control as a critical mechanism protecting against immune dysregulation and cancer.