Nature: Blocking the use of sugar by cancer cells can improve the anti-tumor effect of immunotherapy

Sugar is an important nutrient.
all cells use sugar as an important energy source and building block.
is a good thing for immune cells because it means getting enough nutrients to grow and divide to produce a stronger immune response.
cancer cells use sugar for more evil purposes.
, what happens when tumor cells and immune cells compete for the same sugar supply? Tha Merghoub, Jedd Wolchok and Roberta Zappasodi, researchers at Memorial Sloan-Kettering in the United States, explore this core issue in a new study.
results were published online February 15, 2021 in the journal Nature, under the title "CTLA-4 blockade drives loss of Treg in glycolysis-low tumours."
The researchers used mouse models and data from human patients to find that the amount of sugar consumed by tumors ---in particular glucose--- was directly related to the effectiveness of immunotherapy: the more sugar the tumor consumed, the worse the effect of immunotherapy.
these results suggest that blocking cancer cells' use of sugar may tilt the balance toward immune cells, especially if they are activated by immunotherapy drugs.
Merghoub said, "If we reduce the use of glucose in tumors, then we release more glucose for immune cells, which is good for the immune response."
Wolchok added, "We think we've found a new way to improve immune checkpoint blocking immunotherapy."
" immune checkpoint inhibitors release inhibitions to immune cells and provide lasting benefits to cancer patients, but they are not effective for everyone.
the new study may provide a way to improve its effectiveness.
to study the relationship between the use of glucose by tumor cells and their response to immunotherapy, the researchers used a highly sugar-enzymeized model of breast cancer mice --- which means it uses a lot of sugar to grow.
in the first group of tumors, they genetically inhibited a key enzyme that cells needed to quickly consume glucose during a process called glycolysis.
in the second group of tumors, the enzyme was not affected.
each group of tumors grew in mice, and then treated them with immuno-checkpoint inhibitors for CTLA-4 before surgery was performed to remove the tumors.
their study found that mice with less glucose survived longer and had lower metastasis rates (when the cancer spread) than mice that used more glucose.
showed an improvement in the response to immunotherapy in mice with tumors that consumed less glucose.
addition, the enhanced immune response shows memory.
when the researchers re-implanted tumors in mice that were previously exposed to tumors with less glycolysis, tumor growth was still inhibited.
, mice exposed to more glycolyzed tumors were unable to control the growth of re-implanted tumors.
researchers also studied human data.
when they measured the tumor's use of glucose and compared it with the number of immune cells present in the tumor, they found an inverse relationship between the two measurements.
tumors use glucose, the fewer immune cells are present.
release multiple inhibitors Called immunosuppression, there are two types of T cells that are critical -- effect T cells and regulatory T cells (Treg).
effect T cells are T cells that really attack cancer cells and kill them, while Tregs act as a brake on effect T cells.
that glucose has different effects on these two T cells.
more glucose can improve the lethality of the effect T cells.
for Treg cells, more glucose means they lose the ability to fight effect T cells.
this means that releasing glucose to immune cells has a double benefit to immunotherapy drugs.
Zappasodi said,
Strip it was surprising and exciting to see CTLA-4 blocking inducing Treg cells to use glucose, which in turn reduced the inhibition activity of these cells."
, Dr. Merghoub added, "This means that one way to overcome this resistance is to target tumor glycolysis with drugs for tumors that are highly glyzywys and block non-reactive to immune checkpoints."
the feasibility of using sugar to enhance the immune response depends on the priority given to limiting the use of glucose by tumors--- which is where it becomes tricky.
existing drugs that block the use of sugar by cancer cells also block the use of sugar by immune cells, which can undermine its purpose.
now need drugs that prevent tumor cells from using glucose while lycoal cells are free to use it.
researchers have some clues and are now exploring them.
: 1.Roberta Zappasodi et al. CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours. Nature, 2021, doi:10.1038/s41586-021-03326-4. 2.To improve immunotherapy, researchers look to shift immune cells' access to sugar