Researchers discover how lactic acid weakens anti-tumor defenses
Immune cells feed on lactic acid and paralyze other 'killer' immune cells


Date:
January 30, 2022
Source:
Vrije Universiteit Brussel
Summary:
It has long been known that lactic acid is produced in large
quantities by cancer cells and that this lactic acid disrupts our
defense against tumors. However, scientists did not know exactly
how this happens. Now researchers report they have found the answer.



FULL STORY ==========================================================================
In cancer research, 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 defence against tumours. Until now, however, we did
not know exactly how this happens. Prof Jo Van Ginderachter, immunologist
and cancer researcher at the Vrije Universiteit Brussel and the Flemish Institute for Biotechnology (VIB), found the answer, in collaboration
with PhD student Xenia Geeraerts (VUB), Prof Sarah-Maria Fendt (VIB-KU
Leuven) and Prof Jan Van den Bossche of the University of Amsterdam. The findings were published in the renowned journal Cell Reports.


==========================================================================
Van Ginderachter: "We found that macrophages, a specific type of immune
cells, use lactic acid as a source of energy. Macrophages are present
in large numbers in tumours but are, as it were, misled by the tumour
in order to help it grow.

With the lactic acid of the cancer cells, the macrophages keep themselves
alive but eventually develop into tumour-promoting cells. Under the
influence of the lactic acid, the macrophages paralyse other 'killer'
immune cells that can recognise and destroy the cancer cells, thereby
helping to weaken the tumour immunity." Resistance to immunotherapy
The macrophages thus ultimately contribute to the resistance of tumours
to immunotherapy.

"This strong presence of lactic acid in tumours can have consequences
for immunotherapy," Van Ginderachter says. "In immunotherapy, our body's
own 'killer' immune cells are triggered to optimally attack cancer
cells. Although this therapy is very promising and works very well for
skin cancer and is increasingly used for lung cancer, for example, the
reality remains that only a proportion of patients respond favourably to
it. One of the reasons is probably that macrophages feed on the lactic
acid in the tumour and, as a result, switch off the 'killer immune cells'
that you want to stimulate through immunotherapy.

So we need to be able to suppress immune-disrupting cells, such as
the macrophages, and still increase the success of immunotherapy."
Reducing or neutralising lactic acid production It is therefore important
to look at how the formation of lactic acid in tumours can be curbed. Van Ginderachter points out that lactic acid occurs in large quantities in
many different tumour types.

"Cancer cells typically produce a lot of lactic acid. And in tumours you
also have regions with a 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 tumours. This is a strategy that is already
being investigated in first-stage clinical trials. However, precisely
because we know that in addition to cancer cells, many other cells in
the tumour produce lactic acid, it remains to be seen whether these
strategies will be sufficient to reduce the lactate to such an extent
that its effect on the tumour-supporting macrophages is nullified. On
the other hand, one can try to neutralise lactic acid, for example,
by administering a kind of buffer solution. Preliminary research on
this is also under way. Another option is to use chemicals to ensure
that macrophages can no longer feed on the lactic acid. It is important
that such a substance is not toxic and that it makes its way to the
tumour in a targeted manner. Research is also being carried out in our laboratory into these problems, so that future medicines can be delivered directly to the tumour or the macrophages, thus avoiding side effects." ========================================================================== Story Source: Materials provided by Vrije_Universiteit_Brussel. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xenia Geeraerts, Juan Ferna'ndez-Garcia, Felix J. Hartmann, Kyra
E. de
Goede, Liesbet Martens, Yvon Elkrim, Ayla Debraekeleer, Benoit
Stijlemans, Anke Vandekeere, Gianmarco Rinaldi, Riet De Rycke,
Me'lanie Planque, Dorien Broekaert, Elisa Meinster, Emile Clappaert,
Pauline Bardet, Aleksandar Murgaski, Conny Gysemans, Frank Aboubakar
Nana, Yvan Saeys, Sean C. Bendall, Damya Laoui, Jan Van den
Bossche, Sarah-Maria Fendt, Jo A. Van Ginderachter. Macrophages are
metabolically heterogeneous within the tumor microenvironment. Cell
Reports, 2021; 37 (13): 110171 DOI: 10.1016/j.celrep.2021.110171 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220128141333.htm
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