In oncology, it has long been known that lactic acid, or lactate, is produced in large quantities by cancer cells and that this lactic acid disrupts our defense against tumours. Until now, however, we didn’t know exactly how this happened. Professor Jo Van Ginderachter, immunologist and cancer researcher at the Vrije Universiteit Brussel and the Flemish Institute for Biotechnology (VIB), has found the answer, together with doctoral student Xenia Geeraerts (VUB), Professor Sarah-Maria Fendt (VIB-KU Leuven) and Prof. Jan Van den Bossche from the University of Amsterdam. The results were published in the renowned journal Cell reports.
Van Ginderachter: “We discovered that macrophages, a specific type of immune cell, use lactic acid as an energy source. Macrophages are present in large numbers in tumors but are, so to speak, misled by the tumor in order to help it grow. With lactic acid from cancer cells, macrophages stay alive but eventually turn into tumor-promoting cells Under the influence of lactic acid, macrophages paralyze other “killer” immune cells that can recognize and to destroy cancer cells, thus contributing to weaken tumor immunity. »
Resistance to immunotherapy
Macrophages therefore ultimately contribute to the resistance of tumors to immunotherapy.
“This strong presence of lactic acid in tumors can have consequences for immunotherapy,” explains Van Ginderachter. “In immunotherapy, our body’s own ‘killer’ immune cells are triggered to optimally attack cancer cells. Although this therapy shows great promise and works very well for skin cancer and is increasingly being used for lung cancer, for example, the reality remains that only a proportion of patients respond favorably to it. One of the reasons is probably that the macrophages feed on the lactic acid in the tumor and therefore deactivate the “killer immune cells” that you want to stimulate through immunotherapy. We therefore need to be able to suppress cells that disrupt the immune system, such as macrophages, and further increase the success of immunotherapy. »
Reduce or neutralize the production of lactic acid
It is therefore important to examine how the formation of lactic acid in tumors can be slowed down. Van Ginderachter points out that lactic acid is present in large amounts in many different tumor types.
“Cancer cells generally produce a lot of lactic acid. And in tumors you also have regions of very low oxygen concentration, in which lactic acid can be raised to even higher levels. You can try to prevent the production of lactic acid in tumors. It is a strategy that is already being studied in first-stage clinical trials, but precisely because it is known that in addition to cancer cells, many other tumor cells produce lactic acid, whether these strategies will be sufficient remains to be seen. to reduce lactate to such an extent that its effect on tumor-supporting macrophages is negated. On the other hand, one can try to neutralize the lactic acid, for example by administering a kind of buffer solution. Preliminary research on this is also Another option is to use chemicals to ensure that macrophages can no longer feed on lactic acid. It is important that such a substance is not toxic and goes to the tumor in a targeted manner. way. Research is also being carried out in our laboratory on these issues, so that future drugs can be delivered directly to the tumor or macrophages, thus avoiding side effects. »
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Materials provided by Free University of Brussels. Note: Content may be edited for style and length.