İki yönlü strateji glioblastomanın bağışıklık savunmasını zayıflatıyor

Glioblastoma often resists immunotherapy because its tumor environment disables immune attacks in two ways. Oxygen-starved, or hypoxic, conditions recruit and reprogram myeloid cells that suppress nearby T cells. Meanwhile, T cells that enter the tumor become chronically stimulated and drift toward an exhausted, dysfunctional state. Wistar Institute researchers tested a combination designed to address both barriers in a preclinical mouse model. A low dose of axitinib reduced hypoxia and limited the suppressive behaviour of myeloid cells, allowing more T cells to reach the tumor. Axitinib alone, however, increased median survival from 17 to just 19 days. The team therefore added an agonist targeting the 4-1BB receptor to strengthen cancer-recognising T cells before their exhaustion became terminal. Together, the treatments extended median survival to 42 days, produced 40 percent long-term survival and generated immune memory that resisted later tumor re-exposure. Clinical testing will be needed to determine whether the approach benefits patients.