A
study in mice suggests that by infiltrating tumors and ramping up the body’s
immune response, a type of gut bacteria could be a valuable ally in cancer
treatment.
In
recent years, research has shown that the communities of bacteria that live in
our guts — known as our gut microbiota —
play crucial roles not only in disease but also in promoting health.
Some
research has found beneficial effects of probiotic “friendly” bacteria on the immune system.
For
example, one study suggested that a species of Bifidobacterium can modify the body’s
immune responses in psoriasis, ulcerative
colitis, and chronic fatigue syndrome. Another found evidence that a
combination of Bifidobacteria and Lactobacilli can relieve hay fever.
The
authors of the new study, which features in the Journal
of Experimental Medicine, note that certain bacteria have also
demonstrated the ability to improve the efficacy of cancer immunotherapy by
activating gut immunity.
They
report that in their research on mice, they discovered that various species
of Bifidobacterium can
find their way into gut tumors even after being injected.
Once
inside the tumors, the bacteria seem to activate the wider immune system and,
in the process, enhance a type of cancer treatment called CD47 blockade
immunotherapy.
‘Don’t eat me’
signal
One
of the molecular tricks that tumors deploy to evade attacks by the immune
system is to incorporate a protein called CD47 into their cell membranes.
In
their paper, the researchers describe CD47 as a “don’t eat me” signal to
macrophages, a scavenger type of immune cell that engulfs invading cells,
including cancerous ones. Several ongoing clinical trials are investigating
antibodies that block this signal.
Studies
in models of cancer in mice, however, have found that some of the animals
respond well to these anti-CD47 treatments, whereas others do not.
Interestingly, the mice that respond well have more Bifidobacteria in their feces.
To
investigate further, the team of scientists at the University of Texas and the
University of Chicago ran a series of experiments on mice with cancer.
Contagious effect
First,
they discovered that simply putting mice that did not respond to CD47 blockade
immunotherapy in the same cages as mice that did respond had an effect.
Proximity converted the nonresponders into responders.
When the researchers used
antibiotics to kill off all the animals’ gut bacteria, however, this prevented
mice from responding to the treatment. Conversely, supplementing the
nonresponding mice with Bifidobacteria turned them into
responders.
The
location of the effect seemed to be the tumors themselves, as injecting a low
dose of antibiotics directly into them reduced the efficacy of treatment.
Injecting Bifidobacteria into
the tumors had the opposite effect.
Finally,
the team showed that the bacteria enhanced immunotherapy by activating an
immune pathway called STING (STimulator of INterferon Genes). In mice
genetically engineered to have no STING pathway, Bifidobacteria failed to restore the
effectiveness of immunotherapy.
New avenues for
research
The
lead researchers were Prof. Yang-Xin Fu at the University of Texas Southwestern Medical
Center and Prof. Ralph R. Weichselbaum, co-director of The Ludwig Center for Metastasis Research at
the University of Chicago.
“Our
results open a new avenue for clinical investigations into the effects of
bacteria within tumors and may help explain why some cancer patients fail to
respond to immunotherapy,” says Prof. Weichselbaum.
In
their paper, the scientists suggest that “anaerobic” bacteria such as Bifidobacteria — which do not need
oxygen to survive — may thrive in the low-oxygen environment inside tumors, but
not in healthy tissues.
Several
clinical trials are underway using other anaerobic bacteria, namely Salmonella typhimurium and Clostridium novyi–NT, to destroy tumors.
However, these bacteria are
pathogens. As Bifidobacteria are harmless “commensal” species,
they may be a safer alternative for targeting treatments to tumors or enhancing
immunotherapy.
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