The authors identify syntaphilin as a regulator of spontaneous migration of neutrophils in cancer. Syntaphilin deletion promotes PMN spontaneous migration and metastasis via increased mitochondria motility, elevated rates of oxidative phosphorylation and glycolysis, and increased generation of adenosine.

Immunosuppressive properties of the oral anaerobic bacterium Porphyromonas gingivalis are revealed, highlighting effects of the bacterium that facilitate oral cancer progression. The data suggest that P. gingivalis, and/or signaling it mediates, can be targeted to improve immunotherapy efficacy.

CD161 characterizes an inflamed subset of cytotoxic T lymphocytes that have high expression of immune checkpoints while retaining high cytotoxic capability. These cells can be reinvigorated by immune checkpoint blockade and are a biomarker for clinical benefit.

The authors find that CD161 is overexpressed on a subset of CD8⁺ T cells in chemoresistant breast tumors and drives T-cell dysfunction. CD161 provides a potential target to enhance antitumor immunity and reverse chemoresistance.

How hypoxia-sensing proteins regulate antitumor immunity is incompletely understood. The authors show stabilization of HIF-1α promotes recruitment, survival and/or differentiation of polyfunctional CD8+ T cells into the tumor and synergizes with PD-1 blockade to control tumor growth.

Loss of nitric oxide synthase is shown to debilitate cytotoxic T cells in the therapeutic setting. Although nitric oxide is typically characterized as immunosuppressive, these data highlight its key intrinsic role in modulating T-cell tumor infiltration and suppression.

The authors identify an IL10-producing CD19⁺CD39⁻ immunoregulatory B-cell subset (Breg cells) in breast cancer patients. The Breg cells inhibit H-chain class-switch recombination and generation of antibody-producing B cells by limiting autologous Tfh-cell differentiation and IL21 production.

Cancer cells can become resistant to the antitumor effects of IFNγ. Using high-throughput transcriptomic profiling and CRISPR screens, the authors demonstrate a relationship between the DSB repair pathway and IFNγ resistance, suggesting a potential new combination treatment strategy.