NOVEMBER 28 • 2019 | 53
Boom
D
iversity — at least
among cancer cells
— is not a good
thing. Now, research from the
Weizmann Institute of Science
in Rehovot shows that in mel-
anoma, tumors with cells that
have differentiated into more
diverse subtypes
are less likely
to be affected
by the immune
system, thus
reducing the
chance that
immunotherapy
will be effective.
The findings
of this research, published in
Cell, may provide better tools
for designing personalized
protocols for cancer patients,
as well as pointing toward
new avenues of research into
anti-cancer vaccines.
Prof. Yardena Samuels of
the Institute’
s Department of
Molecular Cell Biology wanted
to know why, despite the
fact that cancer deaths from
melanoma have dropped in
recent years (thanks to new
immunotherapy treatments),
many patients do not respond
to therapy. The reasons have
not been clear, though the
leading hypothesis, supported
by a few studies, has been that
tumors with more mutations
are more likely to respond
to immunotherapy. Some
patients even spend large
sums to undergo radiation
or chemical treatments to
increase tumor mutations, but
a causal relationship between
the two has not yet been
proven.
Samuels and her colleagues
were intrigued by studies
that suggested a different
possible correlation — one
between heterogeneity (that
is, the genetic diversity among
tumor cells) and the response
to therapy. To investigate this
theory, however, the team had
to develop a new experimental
system to check
exactly which
factors play a
role.
“We showed
the difference
between two
extremes
— highly
homogeneous
and highly heterogeneous
— but most cancers fall
somewhere in between,
” says
Dr. Bartok. “To systematically
generate tumors with
intermediate levels of genetic
heterogeneity, we created
a phylogenetic tree of the
parental heterogeneous line,
and mapped out how subtypes
appear over time.
“Then we created ‘
cocktails’
of homogeneous cell lines
based on this tree, with
more or less heterogeneous
combinations of cells, and
injected them into mice.
”
As predicted, the more
homogeneous the cell cocktail,
the easier it was for the mice’
s
immune systems to eradicate
the cancer, whereas the more
heterogeneous the tumors
were, the more aggressive they
became.
“Ultimately, we intend
to use the experimental
system we created to work
on developing applicable
personalized protocols for
cancer patients,” Samuels
said.
Cancer Study
Weizmann researchers work on a
new way to predict treatment outcomes.
WEIZMANN INSTITUTE OF SCIENCE
Prof. Yardena Samuels
DANIEL SHERBERT, M.D. F.A.C.S.
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