How good guys become bad

Scientists have found out how cancer manipulates the immune system

Alexey Yevglevsky, Naked Science

Scientists from the University of Southern California have demonstrated on the example of mice and data from the US National Institutes of Health that cancer tumors are able to use human immune cells for their own protection. The work was published in the journal Cell Reports (Kubala et al., Plasminogen Activator Inhibitor-1 Promotes the Recruitment and Polarization of Macrophages in Cancer).

In previous studies, the university team found that the PAI-1 protein (an inhibitor of plasminogen activation of the first type) is associated with more aggressive forms of cancer. Now the authors have shown that it is his tumor that uses for its protection.

According to the authors, in this work they focused on macrophages – cells of the immune system of animals and humans, capable of capturing and digesting bacteria, the remains of dead cells and other foreign particles. They are important for maintaining tissue homeostasis. 

Previously, scientists assumed that macrophages should fight cancer cells, but experts from the University of Southern California, using the example of mice, showed that PAI-1, through interleukin 6 (IL-6) and the STAT3 signaling protein, is able to convert macrophages into the so-called M2 form, which protects the tumor, and does not attack it.

Graphic image of the manipulation (from an article in Cell Reports).

One of the researchers Yves Albert DeClerck (Yves Albert DeClerck) He explained (in a press release from Children's Hospital Los Angeles When Good Immune Cells Turn Bad) that they saw not only how macrophages protect the tumor, but also how they repair damage after chemotherapy. To find out how widespread this mechanism is among different types of cancer, the authors turned to the Atlas of the Cancer Genome of the US National Institutes of Health, which contains data from 11 thousand patients. According to Dekerk, they found a pattern between the high content of PAI-1 and the appearance of M2-type macrophages in patients with lung, colon, breast cancer and neuroblastoma. Understanding such a reversal mechanism will help develop more effective cancer control strategies in the future.

Prior to this, researchers from the University of Washington discovered in Tasmanian devils sections of genes that contribute to the reduction of DFTD cancer. These data can help to develop a basis for genetic resistance to tumors.

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