PD-L1 is best known as the molecular "off switch" cancer cells use to disable the immune system at their surface. In recent years, however, it has become clear that PD-L1 can also enter the nucleus, yet what drives it there, and what it does once inside, has remained largely a mystery. Researchers from Zhejiang University and the University of Macau now provide an answer: DDB1, a protein adaptor, tags PD-L1 with K63-linked ubiquitin chains at the K185 site—a modification that does two things at once. It removes an acetylation mark that would otherwise keep PD-L1 out of the nucleus, and it enables the nuclear protein to bind DNA and switch on a program of immunosuppressive genes. In breast cancer patients resistant to immunotherapy, this nuclear form of PD-L1 was markedly elevated. Remarkably, thalidomide, an old drug already used for multiple myeloma, disrupts the DDB1–PD-L1 partnership. Combined with anti-PD-1 antibody in mouse models, the therapy shrank tumors dramatically, boosted infiltration of cancer-killing T cells, and extended survival. Published in Science Bulletin, the study uncovers a non-canonical route to immune evasion and offers a "repurposed" combination strategy poised for clinical testing.

The National Institute for Health and Care Excellence (NICE) criteria used to decide who should be referred by GPs for further breast cancer risk assessment and specialist care misses up to 95% of women under 50 who will go on to develop the disease in the next 10 years, new research by researchers at the University of Cambridge and The Institute of Cancer Research, London, has found.

Researchers at the MRC Laboratory of Medical Sciences (LMS), Imperial College London and UCL Genetics Institute have created a detailed map of cells within breast tumours and identified distinct neighbourhoods of proliferating and dormant cells. The study, published in Genome Medicine, reveals that protective immune and connective cells surround the hibernating cancer cells, potentially shielding them from treatments. It suggests future therapies may need to target not only different cancer cell states, but also the local environments that help them survive, to both halt tumour growth and prevent cancer coming back later.