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.

Mayo Clinic researchers have identified a protein that cancer cells use to shut down the body's immune response, a discovery that could help scientists develop new treatments that make cancer immunotherapies more effective.

UCLA researchers have identified a promising strategy to make a new class of targeted cancer therapies more effective against one of the deadliest forms of prostate cancer, potentially overcoming treatment resistance that has limited their success.

About the Study: Does the addition of high-dose vitamin D to standard treatment improve progression-free survival in patients with metastatic colorectal cancer? In this multicenter, double-blind phase 3 randomized clinical trial in patients with previously untreated metastatic colorectal cancer, the addition of high-dose vitamin D to standard treatment did not significantly improve progression-free survival compared with standard-dose vitamin D (median progression-free survival, 11.8 months vs 10.3 months, respectively). High-dose vitamin D did not improve progression-free survival in patients with metastatic colorectal cancer.

A new Houston Methodist-led study reports a breakthrough in understanding why some patients with metastatic breast cancer fail to respond to a common and important early-stage treatment.

VCU Massey Comprehensive Cancer Center was recently awarded a $2.7 million Worta McCaskill-Stevens K12 grant from the National Institutes of Health (NIH). The five-year grant will allow Massey to mentor promising, multidisciplinary, early-stage clinical investigators in the conception, development, and implementation of innovative cancer prevention and control studies designed to optimize participation by cancer survivors and individuals most at risk for cancer throughout Virginia.VCU Massey Comprehensive Cancer Center was recently awarded a $2.7 million Worta McCaskill-Stevens K12 grant from the National Institutes of Health (NIH). The five-year grant will allow Massey to mentor promising, multidisciplinary, early-stage clinical investigators in the conception, development, and implementation of innovative cancer prevention and control studies designed to optimize participation by cancer survivors and individuals most at risk for cancer throughout Virginia.