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posted by takyon on Saturday December 01 2018, @07:05PM   Printer-friendly
from the stop-hitting-yourself dept.

Submitted via IRC for SoyCow1984

When good macrophages go bad: How cancer manipulates our immune system to become harder to treat

Yves DeClerck, MD, of the Children's Center for Cancer and Blood Diseases and the Saban Research Institute at Children's Hospital Los Angeles, has dedicated his career to understanding how cancer cells interact with the surrounding normal tissue to escape the effects of therapy. Research has shown that tumors with high levels of a protein called Plasminogen Activator Inhibitor 1 (PAI-1) are more aggressive and are associated with poorer outcomes. In the new study, published November 20th in the journal Cell Reports, DeClerck's team demonstrated that cancer cells use PAI-1 to trick the body's immune system into supporting the cancer.

DeClerck and his team, led by postdoctoral research fellow Marta Kubala, PhD, characterized a relationship between tumors and the immune system. "In this study, we focused on the role of immune cells called macrophages and how PAI-1 affects their activity," explains Kubala. As important players in the immune system, macrophages find and destroy cancer cells or foreign invaders like bacteria. While macrophages are normally considered anti-cancer, DeClerck's team showed that PAI-1 pushes macrophages into an alternate, pro-cancer state (called M2) by recruiting common players in the immune system -- IL-6 and STAT3 -- effectively signaling to the macrophages to support rather than attack tumor cells.

"A macrophage can either be a friend or an enemy to cancer cells," explains DeClerck, who is also a professor of pediatrics at the Keck School of Medicine of the University of Southern California. "The cancer communicates with the macrophages, telling them to become friendly. So, the macrophages change their behavior and support the tumor." In altering the function of surrounding, healthy tissue, the cancer is better able to survive and spread. The team around DeClerck also shows that cancer cells can use PAI-1 to promote movement of these pro-cancer M2 macrophages into the tumors, where they protect the cancer and repair any damage that chemotherapy may have inflicted. This symbolic one-two punch culminates in a stronger, more difficult-to-treat cancer.

Plasminogen Activator Inhibitor-1 Promotes the Recruitment and Polarization of Macrophages in Cancer (open, DOI: 10.1016/j.celrep.2018.10.082) (DX)


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  • (Score: 1) by javawock on Sunday December 02 2018, @10:30PM

    by javawock (1418) on Sunday December 02 2018, @10:30PM (#768983)

    What we need is a Plasminogen Activator Inhibitor Inhibitor Activator!