IGRs are an ill-studied class of cryptic genomic rearrangements. The authors suggest that IGR burden is a pivotal contributor to immune infiltration and a new genetic biomarker for immunotherapy response in TMB-low, IGR-dominant tumors, and in platinum-exposed tumors.

The authors report single-cell phenotyping of the cHL environment, finding clonal expansion of CD8⁺ T cells and Treg cells. Moreover, conventional T cells retain effector function upon restimulation, arguing against an irreversibly dysfunctional T-cell state in cHL.

By combining an observational analysis of biospecimens and a case series of fecal transplantation, the authors provide evidence for the hypothesis that the intestinal microbiome contributes to the pathophysiology of irColitis and can be remitted with FMT.

Antibodies designed to deplete tumor-infiltrating Tregs have shown limited efficacy in patients so far. The authors identify FcyRIIB as an immune checkpoint limiting the activity of Treg-targeting antibodies in the TME and Fc-engineering strategies to overcome this limitation.

The authors show that Reo-specific NAbs hamper the oncolytic function of Reo but not its T cell–attracting capacity. Since preexisting NAbs are prevalent, this suggests Reo should be used with T cell–based immunotherapies for optimal efficacy.

LILRB3 is an inhibitory receptor expressed by myeloid cells. The authors show galectin-4 and galectin-7 bind LILRB3, promoting the immunosuppressive function of myeloid cells. Blocking LILRB3 reduces immunosuppression and promotes antitumor immunity, suggesting a potential new immunotherapeutic approach.

An NFAT1–complement system feedback loop is identified and shown to induce M2-like polarization of tumor-associated macrophages. Data highlight how these macrophages promote the malignant phenotype of glioma and provide insights into potential complement-associated targets to improve antitumor immunity.