Cytotoxic T lymphocytes responsible for eliminating tumor cells or cells infected by pathogens can form channels through the extracellular matrix, thereby facilitating the arrival of enhancers. German researchers have used synthetic collagen to visualize this process in 3D, and this result can provide new insights for cancer treatment.
In the white blood cell family, Cytotoxic T lymphocytes (CTL, Because of its English abbreviation) plays a key role in eliminating cancer cells and cancer cells that have been infected by pathogenic microorganisms. In order to find the target, they must penetrate the complex microenvironment surrounding the cell: Extracellular matrix (ECM).
In the early stages of disease development, target cells are usually few. Therefore, the ability of these lymphocytes to quickly find and search through them is essential for an effective immune response.
For its part, the matrix is mainly composed of protein substances: collagen. In various types of cancer, the collagen network becomes dense, strong and highly aligned near the tumor, thereby promoting the transportation of cancer cells and making ECM an important factor in tumor metastasis, invasion and prognosis.
In this case, from Saarland University (Germany) They use bovine collagen to generate a 3D matrix and observe how human T cells pass through the matrix.The results are published in Journal of BiophysicsStudies have shown that these immune cells slowly enter the tissue, and then make other CTLs quickly reach the tumor or the infected cells kill them.
The main author of the study said: “The migration behavior of immune cells and their search strategies in ECM have not been well understood. At present, they have aroused great interest in the fields of physics and biology.” Heiko Rieger, He added: “Our results show that the regulatory properties of tissue extracellular matrix will affect the efficiency of immune response, and may provide ideas for new cancer treatment strategies.”
Rieger insists: “Understanding how lymphocytes move and interact in the collagen network is essential to understand the details behind their immune response and design effective treatment strategies.”
To solve this problem and mimic the extracellular matrix, the researchers used three-dimensional networks of different concentrations. Bovine collagen. Then, they used the following tools to visualize and analyze the migration trajectory of human CTL through them: Microscope and image recording The number of living cells in 3D.
Open the road slowly, move fast
Cytotoxic T lymphocytes show three different types of movement: slow, fast and mixed movement.Mathematical model developed by another author Zeinab Sadjadi, Indicating that these units switch between the slow state and the fast state.
There have been previous reports of similar sports Natural killer cell (NK Ø Natural killer) In the collagen present in the target cell. NK cells have immune functions similar to CTL. Rieger said: “The similarity between the characteristics of these T lymphocytes and the trajectory of killer cells suggests that both types of cells can migrate through the common mechanism of collagen networks.”
Based on their observations, the researchers hypothesized that CTL moves slowly when pushing open and tearing collagen fibers to form channels, thereby promoting the rapid movement of other T cells. Experimental evidence confirms this stage. For example, they were found to be behind each other on the same track, and also to move quickly through a cavity similar to an open channel in a matrix.
The authors admit that an important limitation of their research is that they use Synthetic collagen matrix. Therefore, living tissue contains many other components, which may affect the migration behavior of immune cells.
The authors plan to solve this challenge in the future and analyze the long-term effects of T lymphocytes on the extracellular matrix. They will also examine whether the channel enhances the CTL’s ability to search for target cells in the collagen network. Rieger concluded: “Understanding how CTL migrates in these tissues may lead to new therapeutic strategies to prevent early metastasis of cancer.”
Sajadi Wait. “Migration of Cytotoxic T Lymphocytes in a 3D Collagen Matrix”. Journal of Biophysics