PublishedJune 10, 2022, 06:57
The University of Geneva has discovered an unexpected action of certain immunotherapies: not only do they destroy tumours, but also the vessels that transport them.
Immunotherapies remain complex cancer treatments and are only used when traditional methods have proven inconclusive. “Even very promising, these therapies are not miracle solutions and often cause severe side effects. This is why we are working to understand the most minute biological processes”, explains a team of researchers from the University of Geneva who have just made an astonishing discovery on the effects of certain immunotherapies.
It should be noted that, to develop, cancerous tumors feed via blood vessels which provide them with the nutrients necessary for the multiplication of diseased cells, then they migrate via lymphatic vessels to create metastases (name given to a tumor which is propagated elsewhere). When we see the development of these lymphatic vessels in and around a tumor, it is therefore a bad sign.
Block the path without neutralizing the weapon
Therapies aimed at blocking this development of tumor lymphatic vessels (called tumor lymphangiogenesis) have proven disappointing. “Indeed, it is also the way in which dendritic cells, which are cells of the immune system, leave the tumor to activate antitumor T lymphocytes” (which therefore neutralizes a weapon once morest the tumor) explains Stéphanie Hugues, professor associated with the Department of Pathology and Immunology and the Inflammation Research Center of the UNIGE Faculty of Medicine, who directed this work, published in the journal «Science Advances». “We must therefore find a balance in order to inhibit this mechanism without blocking it completely, and to do this decipher in detail its mode of action”.
To do this, the scientists used so-called “killer” T lymphocytes used in immunotherapy protocols. “These T lymphocytes are immune cells specifically activated in the laboratory to eliminate tumor cells, before being injected into patients”, explains Laure Garnier, assistant professor in the laboratory of Stéphanie Hugues and first author of this work. “Here we injected them into mice with melanoma. As expected, the killer lymphocytes destroyed the tumor cells. but they also attacked the lymphatic endothelial cells which line the lymphatic vessels”.
Cells become a new target
How is it possible that these killer lymphocytes, which have only one target, can attack something else? “The destruction of cancer cells leads to the release of tumor antigens. These small tumor elements are then captured by the lymphatic endothelial cells which, having become carriers of tumor identification markers, are also recognized as enemies by the T lymphocytes which attack them. This mechanism therefore makes it possible to disrupt without blocking the lymphatic system associated with the tumor to significantly reduce the risk of metastasis”. A system that therefore fights the tumor and its risk of propagation.
There are several options for destroying these lymph vessels without compromising the action of the immune cells that need them to fight cancer. We can, for example, intervene once immunity has set in, or else in conjunction with therapeutic protocols where the immune system is so strengthened that limiting the development of lymphatic vessels would not alter its functioning. “Nevertheless, our results show that the most effective way is to use killer T lymphocytes generated in the laboratory, and therefore ready to attack, in order to circumvent a first phase of activation which can prove to be problematic”, indicates Stéphanie Hugues. .
Against breast or colorectal cancer
For the research team, exploiting this synergistic effect of “killer” T cells that eliminate cancer cells and destroy tumor lymphatic vessels might increase the effectiveness of treatments once morest cancers where lymphangiogenesis is important, such as colorectal cancer,
melanoma or breast cancer.