16 THE SCIENTIST | the-scientist.com
Masopust of the University of Minne-
sota who was not involved in the study.
“That would be important in the setting
where the tumor has metastasized, which
is often the case.”
To see if something similar would hap-
pen with human tumors, Zloza’s team
implanted human breast cancer cells into
mice’s mammary fat pads. As happens in
this form of human cancer, the fatty tissue
tumors metastasized to the mice’s lungs.
Just as the team had found when working
with mouse tumors, a flu shot into the pri-
mary tumor in the fat pad led to reduced
growth of both that tumor and any meta-
static lung tumors that had started to form.
However, there’s an important dif-
ference between mice and humans that
intrigues both Zloza and Masopust. Lab
mice have never been exposed to the flu,
but humans have, and many get vacci-
nated every year against it. That means
that there could be lingering T cells that
are primed to respond to the inactivated
virus if it’s injected into humans’ tumors.
Masopust and his colleagues have been
studying whether they can use this idea
to tap the adaptive immune system,
harnessing these virus-primed T cells
to quickly target the viral proteins once
the vaccine is injected into tumors and
then spur the immune system to target
the tumors too.
Sure enough, in tumor-bearing mice
that had T cells primed to remember
infection with a particular RNA virus,
injecting a peptide from that virus into
the tumor did jump-start the mice’s
immune system to target the tumor,
Masopust and his colleagues reported
last year (Nat Commun, 10:567, 2019).
The result suggests that in humans,
memory of a flu virus may actually add to
the immune response incited by a viral
injection into a tumor.
Kupper notes that the research also
shows that clinicians could use viral
immunotherapy to boost the effective-
ness of another form of cancer treat-
ment, checkpoint inhibitors, which are
known to be less effective in cold tumors.
“Checkpoint inhibitor therapy, when it
works, tends to work in patients with hottumors, tumors that are already infiltrated
with T cells,” Kupper says. There’s a lot of
interest in turning cold tumors into hot
tumors, and this work on using the flu
vaccine is “a good first step towards that.”
—Ashley YeagerBreaking Away
When Avri Ben-Ze’ev first came across
the cell adhesion molecule L1 in 2005,
the protein was known only for its role
in brain development. It had been linkedto the migration and differentiation of
nerve cells, and to helping axons find
their w ay, but hadn’t been found in cells
outside the brain.
Oddly, though, Ben-Ze’ev, a cancer
researcher at the Weizmann Institute
of Science in Israel, and his colleagues
were finding that the L1 cell adhesion
molecule (L1CAM) was also a target in a
signaling pathway associated with colo-
rectal cancer. Even more unexpectedly,
when the researchers tested the protein’s
effects by loading up human cancer cells
with a virus that made them express theNOTEBOOKLEADING THE CHARGE: Cells at the invading
front of a colorectal tumor express L1 cell
adhesion protein (red).MESRUH TURKEKUL