In a surprising discovery, the researchers found that cells from some cancers escaped destruction by the immune system by hiding inside other cancer cells.
The discovery, they suggested in an article published last month in the journal eVitacould explain why some cancers may be resistant to treatments that were supposed to kill them.
The research began when Yaron Carmi, an assistant professor at Tel Aviv University, was studying what T cells of the immune system may be the most potent for killing cancer.
It started with laboratory experiments that looked at treatment-resistant melanoma and breast cancer in mice, studying why a T-cell attack designed to destroy those tumors didn’t kill them.
I was looking for checkpoint inhibitors, a particular type of cancer therapy.
They involve the removal of proteins that normally prevent T lymphocytes from attacking tumors and are used to treat several types of cancer, including melanoma, colon cancer, and lung cancer.
But sometimes after a tumor seems to have been defeated from T lymphocytes he is recovering.
Carmi, who loves looking at cells under a microscope, began looking at tumors as T cells attacked them.
“I wanted to see the murder, the real murderShe said.
Each time, however, he saw a few giant cells left over after the T cells had done their job.
“I wasn’t sure what it was, so I thought I’d take a closer look,” he said.
The giant cells turned out to be cancerous cells that harbored other cancerous cells, protecting them from destruction.
Once the cancer cells escaped from their hiding places, the T cells were unable to reach them, even though the immune system killed the cancer cells that served as cellular bunkers.
“It was like seeing the devil,” Carmi said.
Cancer cells, he added, can remain hidden “for weeks or months“.
When he removed the T cells from the petri dishes, the cancerous cells came out of their shelters.
He looked at human breast cancer, colon cancer and melanoma cells and saw the same phenomenon.
But blood cancers and glioblastomas, the deadly brain tumors, did not form cell-by-cell structures.
Perhaps, Carmi reasoned, it might be possible to prevent cancer cells from taking refuge.
He decided to examine the genes involved in this defense mechanism.
He found that blocking those genes also blocked the ability of T cells to attack tumors.
“I understand that this is the limit of what the immune system can do,” Carmi said.
“Our immune system cannot win.”
Others, while fascinated by the discovery, say that many questions remain.
“It’s definitely an interesting document with some strong and compelling observations,” said Dr Michel Sadelain, Cancer Center immunologist. Memorial Sloan Ketteringwhere he directs the gene expression and transfer laboratory of the center.
But, he asked, how relevant is the discovery to disabling immunotherapies in the real world?
Dr Marcela Maus, director of the cellular immunotherapy program at Mass General Cancer Center, said the discovery showed what a new defense mechanism for cancer cells could be.
“We’ve seen that tumors can hide from the immune system, including some species of ‘faked’ immune cells, but I don’t think we’ve ever seen cancer cells hiding inside each other.”
But, he added, “I think it needs to be replicated to get the four-wheel drive“.
Dr. Jedd Wolchok, director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, had the same reaction.
“I’ve heard that cancer cells feed on themselves, feed on their neighbors, emit exosomes,” he said, referring to tiny pockets of signaling chemicals.
“I guess this is the next step: hide inside your neighbor.”
One possible remedy, he said, could be to counter cancer cells by treating a patient with immunotherapy for a short time, stopping and then treating again.
This may be in line with emerging questions about how long patients should be treated with these expensive and toxic drugs.
The current advice is to cure for two years.
But, Wolchok said, “a lot of us are asking, ‘Can you get away with less?'”
However, he warned that the immunotherapy used by the Tel Aviv group was not standard in cancer patients.
For now, Wolchok said, while the discovery is “a truly groundbreaking observation,” it remains to be seen whether it will lead to improvements in the treatment of cancer patients.
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Source: Clarin
