Scientists show jet lag conditions impair immune response in mice
Chronic jet lag creates favorable cancer conditions in experimental
models

Date:
October 14, 2020
Source:
Virginia Tech
Summary:
Researchers reveal in a mouse study that chronic jet lag alters
the microenvironment surrounding tumor cells, making it more
favorable for tumor growth, and also hinders the body's natural
immune defenses.



FULL STORY ========================================================================== Imagine you've just arrived in Paris. Your body thinks it should be
midnight - - a restorative time when your cells typically proofread DNA, organize and store energy, and perform other essential chores -- but,
instead, the sun is up and you're awake. On a molecular level, your
cells are stressed, trying to catch up to new environmental conditions.


========================================================================== Shiftwork and experimental models of frequent flying across time zones
have been correlated with cancer risk, but not much is known about how
these circadian disruptions impact the body's ability to curb cancer
growth on a molecular scale.

Now, a new study published today (Wednesday, Oct. 14) in Science Advances reveals that chronic jet lag alters the microenvironment surrounding
tumor cells, making it more favorable for tumor growth, and also hinders
the body's natural immune defenses.

The research, led by corresponding authors Carla Finkielstein, an
associate professor at the Fralin Biomedical Research Institute at VTC,
and Diego Golombek, a professor at the National University of Quilmes
in Argentina, adds to the rapidly growing scientific field of the effect
of circadian disruption on health and wellbeing.

"A key takeaway from this study is that if someone has a proliferative disorder, in this case melanoma, doing shift work or regularly changing
time zones could exacerbate the problem by dampening immune system
response to tumor growth," said Finkielstein, who is also an associate professor of biology in Virginia Tech's College of Science, and director
of the Molecular Diagnostics Laboratory at the Fralin Biomedical Research Institute. "This research also helps explain why some tumors win the
race when a person is exposed to the chronically stressful conditions
that occur when the environment and the body's clocks are misaligned."
Every cell in your body has its own set of molecular clocks -- a series
of genes, proteins, and signaling chemicals that set the pace for
cell growth, division, and decay. In cancer cells, these clocks are
often altered, which allows the tumor to set its own pace for rapid,
unchecked proliferation.



==========================================================================
The body's master timekeeper is located in the brain, where it's entrained
by light and sends signals to synchronize peripheral clocks located
throughout the body. When our perception of day and night becomes muddled
due to irregular intervals of light and dark, our internal clocks and
the environment are misaligned, which, as this study shows, can have
subtle yet significant consequences at a cellular level.

The researchers wanted to know how chronic jet lag impacts the
microenvironment surrounding cancer cells and examined two groups of mice
that were injected with melanoma cells. The first group was exposed to a
normal circadian schedule: 12 hours of light and 12 hours of dark. The
second group's light and dark exposure was shifted by six hours every
two days -- the equivalent of roaming across 21 time zones per week.

A month later, the scientists observed that the tumors in the jet lagged
group were roughly three times the size of the control group.

They also examined samples from the microenvironment surrounding the
tumor, the spleen, which produces immune cells, and the liver. The
researchers found peculiar contrasts in how the immune system responded
to the tumor. For example, the levels of different types of immune cells
called macrophages were inverted to be more prone to accept tumor growth
in the jet lagged group.

Similarly, the rhythms of other immune cells and molecules, including cytokines, were disrupted. Even though the tumors didn't spread into
their neighboring organ, the liver, or the spleen, the scientists
observed that the circadian variations in the immune system in both of
these organs were deregulated.

"We combined two different approaches of chronobiology research to study
the effects of circadian desynchronization on both tumor growth and
immune rhythms, and we found a link," Golombek said. "You need optimal
rhythms in immune cells and immune humoral factors to quell rapid tumor
growth. When circadian rhythms are chronically disrupted, these rhythms
are impaired, inverted, or disappear entirely, which could help explain
why the tumors were significantly larger in the desynchronized group." Finkielstein and Golombek plan to continue studying how immune genes
and cell cycle genes are related in the context of cancer.


========================================================================== Story Source: Materials provided by Virginia_Tech. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. I. Aiello, M. L. Mul Fedele, F. Roma'n, L. Marpegan, C. Caldart,
J. J.

Chiesa, D. A. Golombek, C. V. Finkielstein, and
N. Paladino. Circadian disruption promotes tumor-immune
microenvironment remodeling favoring tumor cell
proliferation. Science Advances, 2020 DOI: 10.1126/ sciadv.aaz4530 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201014141138.htm

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