Surprising discovery: ‘These changes make the tumor recognizable to the immune system’

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“The most important discovery of our work was a stroke of luck,” Susan Kaech, co-author of the study and director of the NOMIS Center for Immunology and Mobile Pathogenesis, told Newsweek. The Salk Institute in San Diego published new results Thursday in the journal Science that show how immunotherapy can be improved to make it more widely available.

“Immunotherapy uses the body’s adaptive immune system to fight the tumor,” Kaech explains. Compared to chemotherapy, immunotherapy is less toxic and more patient-friendly. Its main advantage is that it induces an adaptive immune response against the tumor and can develop long-term immunological memory (against recurrent tumors).

The most important finding was unexpected

However, for reasons that are still unclear, immunotherapy only works in a minority of patients, said Payam Gammage, an expert in mitochondrial oncogenetics at the University of Glasgow. An indication of whether someone is responding to immunotherapy is the condition of their mitochondria – the power plants of the cell. Contrary to previous assumptions, these play an important role in cancer.

The most important discovery came unexpectedly. The scientists programmed the mitochondria to limit the internal energy flow. This resulted in more of the metabolic product succinate, which regulates the activity of genes in the cell. As more succinate is produced, the activity of genes involved in communication with the immune system also increases.

Tumor cells recognizable by the immune system

If these genes are more active, suspicious mutations in the cells can be better recognized by the immune system. In other words, it becomes more difficult for tumor cells to escape the immune system.

“These subtle changes make the tumor recognizable to the immune system,” Kaech explains. What remains a challenge is how to precisely target this mitochondrial rewiring to the tumor cells without increasing toxicity. Although more research is needed, the discovery offers a promising approach for future treatment solutions. (gs)

Source: Blick