1460-C 17 DECEMBER 2021 • VOL 374 ISSUE 6574 science.org SCIENCE
RESEARCH | IN SCIENCE JOURNALS
excitation, cell division, metabo-
lism, and inflammation. The
endocannabinoid system is the
target of phytocannabinoids,
including but not limited to
Δ9-tetrahydrocannabinol (THC)
and cannabidiol (CBD), which
are found in Cannabis sativa. In a
Perspective, Keimpema et al. dis-
cuss the underlying mechanisms
through which phytocannabinoids
and synthesized agents might
function and their potential thera-
peutic applications. Although
there are encouraging results for
endocannabinoid modulation in
some types of epilepsy, there is
much more that must be under-
stood about the functional effects
of phytocannabinoids and their
targets before they can be used
safely and effectively as therapeu-
tics. —GKA
Science, abf6099, this issue p. 1449
CANCER IMMUNOLOGY
An atlas of cancer-
associated T cells
The tumor microenvironment
contains many different kinds
of immune cells, the composi-
tion, function, and roles of which
are unclear. Using single-cell
RNA sequencing of T cells in 21
cancer types from more than
300 patients, Zheng et al. identi-
fied differences in transcript
composition that could be used
to catalog different T cell types
(see the Perspective by van der
Leun and Schumacher). These
annotations identified the dif-
ferent roles of specific types of
CD4+ and CD8+ T cells among
the different tumor types.
Some of these clusters revealed
evidence for two developmental
paths for T cells, one of which
shows a trajectory toward the
“exhausted” T cell state, and an
understanding of this may be
useful in developing future can-
cer immunotherapies. —LMZ
Science, abe6474, this issue p. 1462;
see also abm9244, p. 1446
CORONAVIRUS
Vaccination and disease
The United Kingdom has high
rates of vaccination for severe
acute respiratory syndrome
coronavirus 2 (SARS-CoV-2),
exceeding 80% of adults. As
immunity wanes and social dis-
tancing is relaxed, how are rates
of illness and severe disease
affected by more infectious vari-
ants? Elliott et al. used reverse
transcription PCR data from the
REACT-1 study, which showed
exponential transmission as
the Alpha variant (B.1.1.7) was
replaced by the Delta variant
(B.1.617.2). After adjusting for
age and other variables, vaccine
effectiveness for the new variant
averaged 55% in June and July
of 2020. Despite the slower
growth of the pandemic in the
summer, it looks as if increased
indoor mixing in the autumn will
sustain transmission of the Delta
variant despite high levels of
adult vaccination. —CA
Science, abl9551, this issue p. 1463GENOMICS
Giraffe pangenomes
Genomes within a species often
have a core, conserved com-
ponent, as well as a variable
set of genetic material among
individuals or populations that
is referred to as a “pangenome.”
Inference of the relationships
between pangenomes sequenced
with short-read technology is
often done computationally by
mapping the sequences to a
reference genome. The compu-
tational method affects genome
assembly and comparisons,
especially in cases of structural
variants that are longer than an
average sequenced region, for
highly polymorphic loci, and for
cross-species analyses. Siren
et al. present a bioinformatic
method called Giraffe, which
improves mapping pangenomes
in polymorphic regions of the
genome containing single
nucleotide polymorphisms and
structural variants with standard
computational resources, making
large-scale genomic analyses
more accessible. —LMZ
Science, abg8871, this issue p. 1461