Scientists have found a way to boost the immune response in pancreatic cancer

Scientists from the University of Minnesota Medical School have figured out how pancreatic cancer cells hide from the immune system, and have proposed a way to enhance the antitumor response. In preclinical models, the combination of the two approaches helped to reduce tumor spread and increase life expectancy. This is stated in a study published in the journal Science Immunology.

The authors of the study found that under the influence of immunotherapy, some cancer cells may become less noticeable to the immune system. This is due to the suppression of the Tap1 gene, which is involved in the processing and presentation of tumor antigens. As a result, the work of molecules of the main histocompatibility complex of the first class, MHC—I, is disrupted on the cell surface.

Normally, MHC-I allows immune cells to recognize altered or infected cells. With a lack of these molecules, cytotoxic CD8 T cells are less likely to detect a tumor. Such "invisible" cancer cells are able to evade the immune response and form metastases more often.

The researchers also found that regulatory T cells, which normally restrain excessive immune activity, prevent the destruction of hidden tumor cells by another type of lymphocyte, CD4 T cells. Previously, the latter were primarily considered as auxiliary cells that coordinate the work of the immune system. The new results indicate that they may play a more significant role in the control of metastatic pancreatic cancer.

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In the experiments, the scientists used several ways to release the antitumor activity of CD4 T cells: they removed regulatory T cells, injected lymphocytes capable of recognizing the tumor, and also used immunotherapy directed against the CTLA-4 protein. Each of these approaches helped to contain the formation of metastases in preclinical models.

Therapy against CTLA-4 increased the number of CD4 T cells inside the tumor and promoted the formation of cells with signs of prolonged activity in the tissues. The combination of this method with the restoration of MHC-I, which again made cancer cells visible to the immune system, prolonged the life of laboratory mice.

The scientists additionally analyzed the patient's tumor samples. CD4 cells and regulatory T cells were located side by side, and their number was associated with survival rates. In addition, the gene traits that appeared after exposure to CTLA-4 therapy correlated with more favorable disease outcomes.

The researchers now intend to establish how CD4 T cells coordinate the antitumor response and how this ability can be used to enhance the effectiveness of immunotherapy. At the same time, the proposed strategy has so far been tested mainly on preclinical models, so its safety and effectiveness for patients will have to be confirmed in clinical trials.

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Russian Minister of Health Mikhail Murashko announced on May 28 that child mortality from cancer in Russia has decreased by more than 5% over the past four years. The head of the department noted that lymphoma most often prevails among the identified pathologies. According to Murashko, the measures taken by the state have allowed Russia to reach the European average in this area. He added that infant mortality in Russia has decreased by 27% since 2019.