Science & Technology

Cancer cell nanotubes hijack mitochondria from immune sentinels

AT cells attached to cancer cells (lower right) by nanotubes (upper left)

@ Tanmoisaha

NSAnsel cells send out nanotubes to aspirate mitochondria from immune cells, in a study on November 18th. Nature nanotechnology.. The stolen organelles allow cancer cells to replenish their power while weakening T cells. This is a discovery that may lead to new ways to attack tumors.

“It’s amazing that mitochondrial introduction happened between different cell types, and interestingly between immune cells and cancer cells,” said Ming Tan, a cancer biologist at China Medical University in Taiwan, who was not involved in the study. I wrote in the email as follows. scientist.. Researchers have previously observed mitochondrial migration between cells, but most often they occur between two cells of the same type. “In addition, mitochondrial migration appears to have a significant impact on tumor cells escaping immune surveillance,” Tan adds. “This is exciting. [of] Its potential therapeutic effect. “

look “Nanotubes connect immune cells

Brigham and Women’s Hospital and MIT’s Siradicha Sengputa and colleagues, including co-author He Lin Jiang, came across the behavior of these nanotubes when looking at the dynamics of cancer from a broader perspective. rice field. “What we are trying to do is build a model system to study how cancer cells and immune cells interact using nanotechnology tools, moving to a resolution that is not possible with a light microscope. Is to do. […] And we saw these tubes. Further investigation using a field emission scanning electron microscope reveals a range of these small connectors 3-100 µm long and 50 nm-2 µm wide between cultured mouse and human breast cancer cells and mouse T cells. I did.

Mitochondria (green) migrating from T cells through nanotubes (red) to cancer cells

To determine which cargo passes through the tube, Sengupta et al. Labeled mitochondria with MitoTracker Green and amine-containing molecules in the cytoplasm with CellTrace Far Red. Some cytoplasmic proteins moved slowly between cells, while mitochondria moved much faster. “Trafficking mitochondria was also one-way. About 90% of the traffic goes from immune cells to cancer cells,” says Sengupta. “Obviously, the fact that mitochondrial trafficking is faster means that it is an active process that is happening.”

The team also found that cancer cells cultured with T cells consume about twice as much oxygen as the same cells that grew on their own. This indicates that mitochondria stolen from immune cells promoted metabolism in cancer cells. On the other hand, the respiration of co-cultured T cells was about half that of T cells proliferated alone. “The idea [cancer cells] It can take up local immune cells, borrow mitochondria, and deplete them. .. .. It’s very noteworthy, “said Emil Lou, an oncology scholar at the University of Minnesota School of Medicine who was not involved in the study. “This study opens up the possibility of cancer cells being present .. Not only does it give immune cells an anti-cancer effect, but it also borrows from them and thrives more for immune cells through nanotubes.”

Tan writes that he is wondering if cancer cells are stealing other forms of cargo from immune cells deployed to fight rapidly dividing invaders. “It will be interesting to know that other organelles and other cellular substances other than mitochondria can move through nanotubes and how they affect cancer cells and immune cells. [may be].. ”

look “Cancerous conduit

Currently, there are no specific inhibitors available to block the formation of nanotubes. So, to test how inhibition of mitochondrial metastasis affects cancer cells, researchers instead inhibited Ras / Rho GTPase signaling. It provides the “fuel” for nanotube formation. Indeed, inhibitors blocked the formation of nanotubes in cancer and immune cell cultures, but because Ras / Rho GTPase signaling is involved in gene expression and regulation of cell cycle progression. It may have had other effects on both immune cells, and cell migration.

However, when researchers injected the inhibitor alone into a mouse model of human breast cancer, tumor growth did not decrease. Scientists have observed a decline in growth when Ras / Rho GTPase inhibitors are combined with PD1 inhibitors, immunotherapeutic agents that prevent cancer cells from “silence” immune cells. Sengupta points out that not all patients currently respond to such drugs. “Maybe in those patients, the tumor sucks out mitochondria and closes. [the immune cells] under. .. .. .. If it can be prevented, the number of immune cells in the tumor will increase. That is the goal. “

Sengupta wrote in an email that he and his colleagues at Brigham and Women have applied for a patent for a more specific inhibitor of nanotube formation. Sengupta also co-founded Invictus Oncology with Akamara Therapeutics. Both are actively pursuing immune-based cancer treatments.

Lou states that the hypothesis that the tumor-reducing effect of Ras / Rho GTPase inhibitors in mice derives from the prevention of nanotube formation requires stronger support. “It’s the exact effect that occurred in the mouse model. It’s hard to say that it was caused by nanotubes based on the data provided,” he said, although he considers the study to be “very detailed.” He added that there is a lack of compelling in vivo evidence that nanotubes are formed within the tumor.

Cancer cell nanotubes hijack mitochondria from immune sentinels Cancer cell nanotubes hijack mitochondria from immune sentinels

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