In a first-of-its-kind research breakthrough, a team of scientists at the University of Massachusetts Amherst has analysed and described what they call the “mosquito effect,” which sheds light on how certain pathogens, such as cancerous tumour cells, can outwit the body’s immune system.

Just as mosquitoes ingest their host’s blood, the immune system’s T cells incorporate cytoplasmic material from tumours into their own cytoplasm.

While it has long been known that many kinds of cells can transfer cellular material from one to another, the transfer of the cytoplasm has never been observed in T cells.

Subsequent single-cell RNA (scRNA) sequencing shows that cytoplasm from tumour cells alters the machinery responsible for protein coding in the host T cell.

The research, reported recently in the journal Frontiers in Immunology, is a major step forward in understanding how tumours can successfully evade the immune system, and thus a step toward more effective treatments.

One of the great mysteries in medicine is how certain pathogens can suppress the immune system in order to spread wildly.

There are many different parts to the immune system, but among the most important are T cells, which identify and attack pathogens, and the T regulatory cells, which tell the T cells when it’s safe to call off the attack, limiting collateral damage to the body.

And yet, cancerous tumour cells have figured out how to short-circuit the immune system, with often catastrophic results for healthy tissues.

How, exactly, tumour cells do this is unknown, but, says Leonid Pobezinsky, associate professor of veterinary and animal sciences at UMass Amherst and the paper’s senior author, “we’ve observed for the very first time that T cells and T regulatory cells suck up a bit of tumour cytoplasm and integrate it into their own.”

To make the discovery, Pobezinsky and his team, including first author Kaito Hioki, graduate student in veterinary and animal science at UMass Amherst, and Elena Pobezinskaya, research assistant professor also in veterinary and animal sciences at UMass and co-senior author of the paper, engineered tumour cells to produce an ultrabright fluorescent protein called ZsGreen.

They then introduced the green-glowing tumour cells into a mouse model.

After eight days, the model’s tumour-infiltrating immune cells were gathered and analysed using state-of-the-art equipment in the Flow Cytometry lab at UMass Amherst’s Institute for Applied Life Sciences.

“What we saw was striking,” says Pobezinskaya. “The T cells were glowing and uniform green, which tells us that that the tumour’s cytoplasm had been distributed widely throughout the T cell.”

Even more surprising was to see the T regulatory cells light up as well. And the team found that the cells glowing the brightest were the ones most exhausted from their fight against the tumour.

Finally, the team determined that the transference of cellular material requires the cells of the tumour and the immune system to come into physical contact with each other.

“We know that tumour cells use multiple ways to suppress the immune system,” says Hioki. “We also now know that T cells incorporate some of the tumours in their own cytoplasm, and that the least aggressive immune cells have the most tumour cytoplasm in them. What we don’t know is why. Are the T cells looking for food? Are they trying to survey and adapt to their new environment by taking in parts of other cells? And finally, is the tumour hijacking this mechanism to shut down T cells?”

These questions are all next steps for the authors, whose work was supported by the National Institutes for Health and the National Research Service Award.

Source: University of Massachusetts Amherst