Waging War on Cancer with the Sword of Immunity
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چکیده
Tumors anda fully armed immune systemdonot get along. To shield themselves from external attack, tumor cells induce an immune-suppressive local environment, and regulatory T cells (Tregs) are their favorite targets. Ali et al. (2014) discover that PI(3)K p110d is a focal point of attack. The authors first examine the effect of p110d genetic inactivation on cancer development in mice, and they observe a strong inhibition on both tumor growth andmetastasis in various tumor models. A closer look at the immune system reveals that p110d inactivation preferentially impairs themaintenance and activity of Tregs in the periphery, rendering tumors vulnerable to the attack of cytotoxic T lymphocytes (CTLs). Interestingly, p110d inhibitors have recently been shown highly effective in treating patients with certain types of leukemia and lymphoma, presumably through targeting cancer-stroma crosstalk. The authors now find that treatment with these inhibitors fully recapitulates the beneficial effect of p110d inactivation in their models, not only indicating the potential of repurposing these clinically effective drugs for treating various solid tumors but also providing valuable insights on the role of p110d in modulating immune environment in the tumor context. Notably, a mild defect of differentiation from CD8+ T cells to fully competent CTLs is observed with the treatment. Strategies to further minimize the impact of p110d inhibitors on CD8+ T cell differentiation while restraining Treg activity may be a future direction to pursue. Ali, K., et al. (2014). Nature 510, 407–411.
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عنوان ژورنال:
- Cell
دوره 158 شماره
صفحات -
تاریخ انتشار 2014