Blood Cancers are Outsmarting the Immune System, But How?
Researchers have discovered how some of the blood cancers known as myeloproliferative neoplasms (MPNs) evade the immune system. Their findings reveal that a subset of MPNs might be susceptible to treatment with immune checkpoint inhibitors that specifically target the PD-1/PD-L1 pathway (a signaling network that normally functions as an "off switch" that blocks T cells from attacking other cell types), such as the currently marketed therapies Keytruda™ and Tecentriq™.
Certain cancers hijack the PD-1/PD-L1 pathway to prevent T cells from eradicating malignant cells, and scientists have remained uncertain if MPNs (a group of diseases where bone marrow makes too many red blood cells, white blood cells or platelets) avoided the immune system through similar mechanisms. Many patients with MPNs have abnormally activated versions of a signaling protein named JAK2, and Alessandro Prestipino et al. determined that the mutant molecule helps activate PD-L1 production – exposing a potentially promising therapeutic vulnerability. In a patient with the MPN polycythemia vera who had undergone a stem cell transplant and subsequently relapsed, treatment with an anti-PD-1 checkpoint inhibitor led to improved symptoms.
Anti-PD-1 therapy was also effective in mice with MPNs. Interestingly, T cells from healthy donors growing in culture together with JAK2-mutant cells turned down gene expression for growth and energy production – a result consistent with the observation that mutant JAK2 drives immune cell exhaustion. Prestipino and colleagues further tracked down the specific proteins that partnered with mutant JAK2 to boost PD-L1. The authors speculate that cancer-driving mutations might cooperate with similar immune-escape mechanisms in other cancers.
This article has been republished from materials provided by AAAS. Note: material may have been edited for length and content. For further information, please contact the cited source.
Macrophage's Role in Maintaining Tattoos Could Hold Key to RemovalNews
Researchers have discovered that, though a tattoo may be forever, the skin cells that carry the tattoo pigment are not. Instead, the cells can pass on the pigment to new cells when they die. The study suggests ways to improve the ability of laser surgery to remove unwanted tattoos.READ MORE
Neuroblastoma Biomarker Research Advances TreatmentNews
Neuroblastoma, a childhood cancer, is treatable in less than half of aggressive cases, but new RNA biomarkers may help identify high-risk patients faster and lead to better prognosis.READ MORE
New Causes of Cellular Decline in Prematurely Aging Kids DiscoveredNews
In a recent paper published in Cell Reports, Saint Louis University researchers have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. The data points to cellular replication stress and a mistaken innate immune response as culprits, and the team found success in the laboratory in blocking these processes with vitamin D.READ MORE