This video shows two immune cells with congruent traces moving in collagen. (Credit: Sadjadi et al. Biophysical Journal)
The immune system apparently has “pioneers” who pave the way for subsequent “combat troops”, according to a study: According to a study, some cytotoxic T lymphocytes drill tunnels in the so-called extracellular matrix that can surround cancerous tissue. Further defense cells can then move particularly quickly through these channels and thus better reach the enemy. Such insights into the behavior of the body police could advance the development of cancer therapies, the scientists say.
Cells in our body are constantly degenerating. If the immune system does not eliminate them effectively enough, they can develop into tumors and lead to life-threatening cancer. It is therefore important that degenerated cells are recognized and destroyed as early as possible. The cytotoxic T lymphocytes play a key role in this. These defense cells patrol through the tissues of our body and use certain characteristics to check the condition of cells in order to kill those that pose a threat to the organism. To find their targets, they have to move through complex biological microenvironments. These are mostly shaped by the extracellular matrix that surrounds cells and consists mainly of collagen. In various types of cancer, the collagen network near tumors becomes dense and stiff.
Tracking down immune cells
“The movement behavior of the cytotoxic T lymphocytes and their search strategies in the extracellular matrix are not yet well understood and are currently of great interest,” says Heiko Rieger from Saarland University in Saarbrücken. “Understanding how CTLs migrate in such tissues could lead to new therapeutic strategies for preventing metastasis in early cancer stages,” says the scientist. In order to study how these immune cells move, he and his colleagues created replicas of the extracellular matrix from bovine collagen. In this experimental tissue, they then analyzed the movement behavior of human cytotoxic T lymphocytes using microscopic examinations.
As the results initially made clear, the immune cells have three different gaits: slow, fast and mixed. According to the researchers, it is becoming apparent that there are no slower and faster specimens, but that the cells can switch between gaits. These results led to the speculation that the cytotoxic T lymphocytes move slowly in a special function: when they push collagen fibers aside to create channels in the extracellular matrix that may facilitate other T cells to move around the network. The researchers were then able to substantiate this explanation through subsequent observations. It was shown that migrating T cells can follow one another on exactly the same path. Successors move particularly quickly in the channel-like cavities within the collagen matrix, say the researchers.
Pioneers in the fight against cancer
The results suggest that the body’s defense system has analogies to military tactics: Before an attack can be successfully carried out in impassable terrain, the pioneers first step up and prepare the way for the combat troops. In the case of the immune system, this means that slowly progressing cytotoxic T lymphocytes dig tunnels in the extracellular matrix through which other immune cells can move very quickly. Using these unobstructed abbreviations, they can then reach tumor cells comparatively quickly in order to destroy them.
According to the researchers, their assumptions are also supported by earlier evidence that another “unit” of the immune system – the so-called natural killer cells – also exhibit similar movement patterns. “This indicates a common mechanism for the migration of both cell types through collagen networks,” says Rieger.
He and his colleagues now want to stay on the ball: They will investigate more closely whether the channels actually improve the ability of the cytotoxic T lymphocytes to search for target cells in collagen tissues. They also want to analyze the long-term influence of T cells on the extracellular matrix. The team hopes that the insights into the movement behavior of immune cells in the body could contribute to the development of new approaches in the fight against cancer. “Our results suggest that a change in tissue has an influence on the efficiency of the immune response and could thus generate ideas for new therapeutic strategies in cancer treatment,” says Rieger.
Source: Cell Press, Saarland University, specialist article: Biophysical Journal, doi: 10.1016 / j.bpj.2020.10.020