How blood cancers outsmart the immune system

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


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