Potential markers of immunotherapy success in the treatment of lung cancer

Lung cancer has the highest mortality rate of all cancers, and treatment options are very limited, especially in patients with carcinogenic mutations in the KRAS gene. While great expectations have been placed on the approval of immune checkpoint inhibitors, in reality, some patients respond very well to this treatment, while others have no effect at all.In a treatise just published in Scientific translation medicineThe MedUni-Vienna research group, led by Herwig Moll (Center for Physiology and Pharmacology), identified potential markers of immunotherapy success in lung cancer patients and explained the underlying molecular processes.

KRAS is a monomeric G protein that plays an important role in the growth of malignant tumors. KRAS mutant lung cancer occurs frequently in chronically inflamed lungs, especially heavy smokers.The inflammatory process promotes growth cancer cell. Research groups now show that the expression of the highly anti-inflammatory protein A20, which is formed in the body, is often very low in these. Malignant cells And there is a direct correlation between life expectancy of patients and expression of this protein. The mall explains: “In both human and animal models, loss of A20 leads to reduced immune surveillance of cancer cells. Cancer cells with low levels of A20 can escape detection by the immune system.” This allows tumor growth. Will be significantly faster.

In the course of this study, co-sponsored by MedUniVienna’s Cancer Research Initiative and related to the Comprehensive Cancer Center Vienna, the research team discovered that it was primarily an increased susceptibility of cancer cells to the immunomodulatory cytokine interferon gamma. did. I am responsible for this. In addition, A20 downregulated tumor cells responded particularly well to immune checkpoint inhibitors, as did patients suffering from melanoma (skin cancer) with a similar gene expression structure.

“At A20, we discovered a previously unknown tumor suppressor. lung cancerLoss as an immune checkpoint contributes to the development of this malignancy, “explains Emilio Casanova, co-author of the Institute of Pharmacology. Patients with low A20 expression have little immunity to fight the tumor. cell Therefore, in the advanced stage, these patients may be excluded from immunotherapy for PD-L1 because they rarely express the important immune checkpoint molecule PD-L1. In fact, the strength of expression of this molecule is currently regarded as an aid in deciding whether to treat with immune checkpoint inhibitors. “Based on our results and the data obtained from melanoma patients, we are confident that we have identified a group of lung cancer patients who will really benefit from this immunotherapy. Excluding them from such treatments would be such. Patient survival is significantly reduced. “

In further research, researchers want to see if it is possible to manipulate the expression of A20. cancer cell, To enhance the effect of immunotherapy. “But smoking is still the easiest risk factor to avoid. lung cancer. Therefore, we must uphold the law to protect the general public from the inhalation of harmful smoke, while at the same time exercising the personal responsibility of those who refrain from smoking altogether, “says Mohr. A new therapeutic approach to improve the quality of life and survival potential of affected people.