Obesity has been associated with cancer for quite some time now, although the complete scenario still eludes researchers.
Now, a new Harvard study underscores some missing parts of this important information, discovering that cancer cells the higher availability of fat to starve immune cells of fuel and hinder them from targeting tumors.
High-fat diets are recognized for increasing the danger of many cancer types and reducing therapeutic outcomes, not to mention survival rates.
For example, a New Atlas report indicates, previous research has found that obesity may activate metastasis in "otherwise benign cancers," and fatty tissues can offer "hideouts" for cancer stem cells, enabling them to "come roaring back" following chemotherapy.
However, it is not that simple either; the said report specifies, inconsistently, obesity seems to enhance results for some types of treatments for cancer.
High-Fat Diets
In this new research, scientists at Harvard found that high-fat diets appear to lessen the amount of CD8+ T cells, including their abilities to fight cancer. Accordingly, when fat becomes more readily available, tumors will renew their metabolism to eat up.
Meanwhile, the high-energy content fast-tracks their growth while simultaneously depriving T cells of fuel that could be otherwise used to combat cancer.
According to the study's co-senior author, Arlene Sharpe, "We know there is a metabolic tug-of-war between tumor cells and T cells that changes with obesity."
In connection to this, the co-senior author added, their study offers a road to discover this link, which can help them to start thinking about cancer immunotherapies and combination treatments in new ways.
Study in Mice
The research team investigated this multifaceted relationship in mice that had different cancer types by providing some groups with high-fat diets and comparing the microenvironments around their tumors to mice that ate normal diets.
As a result, the study authors found that tumors developed more rapidly in obese mice, although interestingly, it was only applicable for mice that had immunogenic cancers, those that the immune system reacts to more readily.
Furthermore, the scientists noticed, too, that the tumor found in the microenvironment contained lesser free fatty acids, even though their quantities were quite high throughout the rest of the body.
This then prompted the researchers to search to discover that the cancer cells were This led the team to discover that the cancer cells were increasing their uptake of fat, leaving nothing for the CD8+ T cells.
In other assessments, when the researchers removed CD8+ T cells from mice, their diet did not affect the rate of growth of tumors anymore.
Through further research, the scientists zeroed-in on PHD3, a protein which, in normal cells, is slowing down fat metabolism.
Levels of PHD3 were found to be substantially lower in cancer cells in environments with obesity compared to the opposite. When researchers overexposed this said protein, they became more slowly and could not eat up much fat.
Cancer Immunotherapy Improvement
The researchers said the new findings could help in the improvement of cancer immunotherapy. After all, they said, "the CC8+ T cells are used in CAR-T cell therapy," where samples of immune cells of a patient are taken out, modified against cancer, and introduced again to the body.
On the other hand, PHD3, or any other related protein, could turn into a new treatment target. The research finding could help customize too, other cancer treatments for obese individuals.
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