Saturday, May 28, 2022

Cancer Thwarts Immune Cells by Donating PD-1 When Attacked

Cancer is a beast with many heads, but it will be history one discovery at a time!

"... NK cells, also known as large granular lymphocytes, engage tumor cells in a process called trogocytosis, which involves stealing part of their target’s membrane and integrating it into their own. The new study, published today (April 13) in Science Advances, shows in mice with leukemia that this nibble sometimes comes with a side of PD-1, a protein that inhibits NK cell activity, allowing the cancer cell to escape.
When an immune cell such as an NK cell or a T cell encounters PD-1 on the surface of a cancer cell, its activity is subdued. PD-1 is thus a common target of cancer immunotherapies, which aim to rev up the body’s own defenses against the disease. ..."

From the abstract:
"Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8+ T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 on the surface of NK cells, rather than being endogenously expressed, was derived entirely from leukemia cells in a SLAM receptor–dependent fashion. PD-1 acquired via trogocytosis actively suppressed NK cell antitumor immunity. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where NK cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and cytotoxic T cells, reveal the immunoregulatory effect of membrane transfer occurring when immune cells contact tumor cells."

Cancer Thwarts Immune Cells by Donating PD-1 When Attacked | The Scientist Magazine® New research in mice reveals why natural killer cells, normally effective at hunting cancer, are sometimes stopped in their tracks.  

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