SCIENCE science.org 3 JUNE 2022 • VOL 376 ISSUE 6597 1065-C
RESEARCHthat whereas environmentally
realistic exposure levels were not
directly lethal, they did result in a
decrease in the ability of colony
members to maintain their
required hive temperatures (see
the Perspective by Crall). Such
nonlethal effects can have perni-
cious effects that lead to indirect
decline in this already challenged
group. —SNV
Science, abf7482, this issue p. 1122;
see also abq5554, p. 1051
CANCER
Shifting kinase duties in
blood cancer
Mutant forms of the kinase BTK
promote the growth of chronic
lymphocytic leukemia and other
B cell malignancies. Resistance
to the BTK inhibitor ibrutinib can
arise through acquired muta-
tions at the drug-binding site
of BTK. Dhami et al. character-
ized two such mutations that
mediate ibrutinib resistance.
The phosphorylation of these
BTK mutants upon B cell recep-
tor stimulation enabled their
interaction with and autoactiva-
tion of the kinase HCK. HCK then
phosphorylated the downstream
effector of wild-type BTK that
promoted cell proliferation.
—LKF
Sci. Signal. 15 , eabg5216 (2022).
CANCER IMMUNOLOGY
B and T cells tag team
cancer
Understanding how cancer
immunotherapy induces absco-
pal effects, shrinkage of tumors
that are not the direct target,
is crucial to optimizing future
cancer treatments. Sagiv-Barfi
et al. used a two-tumor mouse
model to show that treatment
of only one tumor with CpG
(a Toll-like receptor 9 agonist)
and interleukin-12 fused to Fc
induced abscopal responses.
These abscopal responses were
dependent on both B and T cells;
B cells in the periphery produced
antitumor antibodies, and B cells
from the tumor-draining lymph
node directly presented antigen
to antitumor T cells. The addition
of an agonistic anti-OX40 anti-
body to the treatment induced
profound antitumor responses
of treated and abscopal tumors.
—DAE
Sci. Immunol. 7 , eabn5859 (2022).