 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.
Certifi
 ed by The American Board of Surgery, 
The American Board of Plastic Surgery & Fellowship 
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Specializing in Cosmetic Surgery &

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