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Cancer cells and immune cells have something in common: they both like to eat 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 supply of sugar? 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."
Using mouse models and data from human patients, the researchers found 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.
If we reduce the use of glucose in tumors, then we will release more glucose for use by immune cells, which is good for the immune response," said Dr. Meghoub.
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 the response to immunotherapy, the researchers used a highly sugar-ionized mouse model of breast cancer --- 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 were treated with immuno-checkpoint inhibitors for CTLA-4 before surgery was performed to remove the tumor.
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, enhanced immune responses show 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 of multiple inhibitors called immune checkpoint blocking, 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.
means that releasing glucose to immune cells has a double benefit to immunotherapy drugs.
Zappasodi said, "It is surprising and exciting to see CTLA-4 blocking induce Treg cells to use glucose, which in turn reduces 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-responsive 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 improvetherapy, researchers look to shift immune cells' access to sugar This article is sourced from Bio Valley, for more information please download Bio Valley APP (