How a tumor blocks dendritic cells
Scientists have established how cancer cells bypass immune defenses
American biologists have found out why dendritic cells, whose functions include pathogen recognition, sometimes ignore cancer cells, allowing them to multiply unhindered. The results of the study are published in the Journal of Experimental Medicine (Fein et al., Cancer cell CCR2 orchestrates suppression of the adaptive immune response).
The main function of dendritic cells, an important element of the immune system, is local immune surveillance. They detect antigens that have entered the body and deliver them to killer T cells. This process is called presentation.
After that, the body usually begins to produce its own antibodies against foreign potentially dangerous substances. Immune protection against cancer cells should be built according to the same scheme, but this does not happen.
Scientists from the Cold Spring Harbor Laboratory (CSHL) decided to find out why dendritic cells do not perform their functions in oncological diseases. Breast cancer was chosen as an example.
The researchers found that cancer cells produce a protein on their surface called the C-C chemokine receptor 2 (C-C chemokine receptor type 2, CCR2). CCR2 molecules suppress the secretion of a signal necessary for the cross-maturation of dendritic cells. Not maturing, they cannot do their job – deliver fragments of cancer cells for presentation to T-killers. Thus, cancer cells avoid detection by the immune system, which leads to unnoticeable and unhindered tumor growth.
Micrographs of mouse tumors. On the left, cancer cells (green) contain the CCR2 protein, and there are few dendritic cells (red) in this tumor; on the right, a tumor in which cancer cells do not contain the CCR2 protein. The cell nuclei are colored blue in both images.
Such a mechanism was a complete surprise to scientists. The fact is that the CCR2 protein is present in the immune cells themselves, but performs a completely different function there. Immune cells use it to move in areas of inflammation.
In 2012, the laboratory headed by associate Professor Mikala Egeblad, the head of this study, has already shown that blocking CCR2 on immune cells can improve the ability of drugs to penetrate tumors, but biologists did not figure out the mechanism of action of this receptor at that time.
Currently, CCR2-blocking drugs are undergoing clinical trials as a cancer treatment. The results of the new study provide insight into how cancer cells use CCR2 to suppress key proteins.
"In fact, no one has delved into the mechanism of CCR2 blocking itself before," the words of the first author of the article Miriam Fein are quoted in the laboratory's press release. "This opens up new opportunities for creating more effective drugs and cancer treatments."
Blocking the activity of CCR2 produced by cancer cells, according to the authors, will help the body initiate its own immune response and fight the tumor more actively.
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