182 deceivers
Immune system Cheating Genes Found in cancer cells
Canadian scientists have identified 182 genes that allow cancer cells to avoid death when encountering the immune system. Thanks to this discovery, cancer immunotherapy can become more effective. The results of the study are published in the journal Nature (Lawson et al., Functional genomic landscape of cancer-intrinsic evasion of killing by T cells).
Biologists from the University Toronto studied the genetic characteristics of six types of tumors of the breast, colon, kidney and skin. Scientists have mapped the genes that regulate the interaction between cancer and immune cells, identifying among them those that allow cancer to hide from the immune system.
"Over the past decade, immunotherapy has become a fairly common method of cancer treatment. But in reality, they cause a persistent response only in some patients, and not for all types of tumors," the words of the head of the study, professor of molecular genetics Jason Moffat, are quoted in a university press release.
In immunotherapy, the patient's own immune cells, known as T-killers, are used to fight cancer. The discovery, according to the scientist, will allow the development of immunotherapeutic methods that are effective for large groups of patients and different types of tumors.
The study also revealed the need to take into account the genetic composition of tumors in immunotherapy, especially those mutations in cancer cells that can potentially worsen the disease in response to treatment. They are called resistance mutations.
"It is very important to understand at the molecular level how cancer forms resistance to immunotherapy," Moffat notes.
The task is complicated by the heterogeneity of tumors – their genetic variability, which in each case determines the individual characteristics of the immune response.
"It is important not just to find genes that can regulate immunity evasion in one cancer model, but those genes that can be manipulated in cancer cells in many models. They will be the best therapeutic targets," says another participant in the study, Keith Lawson.
The researchers placed the cancer cells in a cup next to the T cells and measured the initial level of the immune response. Then, using the CRISPR gene editing tool, they alternately turned off each gene in cancer cells and measured deviations from the baseline.
As a result, biologists identified 182 genes, which they called "the main genes of internal evasion from immunity." By controlling these genes, scientists made cancer cells more sensitive or more resistant to the attack of T-killers. Many of the genes found previously had no connection with immunity evasion.
The authors hope that in the future it will be possible to determine the most effective type of therapy in each specific case based on tumor DNA.
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