Why good viruses don’t always kill cancer

US, WASHINGTON (ORDO NEWS) — Researchers from the “tumor laboratory” at the London Institute for Biomedical Research Francis Crick presented the results of a new work in which they answered an important question: why “good” viruses do not always fulfill their purpose and do not kill cancer cells.

Therapeutic oncolytic viruses – a new direction in the treatment of malignant tumors, which received its own name: virotherapy. Unlike the well-known coronavirus, oncolytics are good viruses, a real “miracle miracle” of modern science. They are designed to infect and destroy only cancer cells , with minimal impact on healthy tissue cells. This is their main difference from traditional methods of cancer therapy, causing many adverse reactions.

Viral oncolytics were first tested in the 1990s, although the idea itself and attempts to realize it date back to the beginning of the twentieth century. In 2015, just five years ago, the US Department of Food and Drug Administration approved the use of virotherapy for certain types of cancer . However, the development of this promising and inexpensive method of treatment development slows down in many respects, no, not only the pharmaceutical lobby and not the fear of viruses as such, but an incomplete understanding of what is happening.

Biologists and doctors noticed that oncolytics do not work for all patients, and until recently they could not understand the reason for such selective effectiveness. Therefore, they could not evaluate the effectiveness of virotherapy in general.

For a better understanding of what is happening, the researchers observed the microenvironment surrounding the tumor, and how the cancer cells interact with their neighbors, in particular, cancer-associated fibroblasts (CAF, cancer-associated fibroblasts).

Normally, fibroblasts perform a protective function, inter alia, limiting the growth of tumors. However, CAFs behave like defectors , protecting malignant cells rather than healthy ones. Researchers are aware that CAFs – “reprogrammed” cancer fibroblasts – become part of the defense mechanism of tumors and play an important role in their growth and metastasis (spread).

During a new study, scientists found that when a cancer cell comes in direct contact with CAF, an inflammatory reaction occurs that puts the surrounding tissue in a “high alert mode”. Oncolytic virus, encountering such resistance on its way, can no longer effectively crack the defense and penetrate the cancer cell (which in itself has a weak immunity). Even if the virus succeeds, its multiplication in the tumor cell occurs less intensively or does not occur at all. Therefore, it is not possible to achieve lysis (destruction of the host cell by the proliferated viral “progeny”) and the whole point of such an intervention disappears.

As scientists have found out this time, such a protective (for the tumor) inflammatory reaction occurs when cancer cells transmit CAF a small amount of cytoplasm, the semi-liquid contents of the cells. This causes fibroblasts to signal to surrounding cells that it is time to release cytokines – proteins that activate the immune response to inflammation.

This paragraph in a press release by the Francis Crick Institute is provided with an asterisk underneath which contains several additional lines for advanced readers: Transfer of the cytoplasm from cancer cells to fibroblasts activates STING molecules (ST imulator of IN terferon Genes, interferon gene stimulator) and IRF 3-dependent expression of interferon beta-1 and other cytokines.

“This process only happens when cancer cells and fibroblasts are in direct contact with each other. In healthy tissues, this type of inflammatory reaction is only observed with traumatic injury, since the membrane usually prevents direct contact. This is a good example of how cancer breaks into protective mechanisms of the body for their own benefit”, – said Erik Sahai, lead author of the research paper and the head of the research team.

When researchers blocked the signal transmission path in cell cultures and tumors grown in the laboratory, this increased the sensitivity of cancer cells to oncolytic viruses.

Scientists hope that the results will help develop a therapy that would reduce the inflammatory response, allowing cancer cells to more effectively affect cancer cells.

“If we could better understand how cancer cells protect themselves from viruses and find effective ways to break into our own defense mechanism, then oncolytic viruses would be a powerful tool in the treatment of cancer. Our study is one of the first important steps in this direction.” – said Emma Milford, co-author of the study.

Researchers plan to continue work and further focus on studying the mechanism of cytoplasmic transfer between cells.

The results are published in Nature Cell Biology.


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