Scientists identify potential new 'soldier' for cancer immunotherapy
Date:
April 20, 2022
Source:
Memorial Sloan Kettering Cancer Center
Summary:
The new cells, which the scientists have dubbed killer innate-like T
cells, differ in several notable ways from the conventional target
of many immunotherapies.
FULL STORY ========================================================================== Despite the success of immunotherapy in helping many people with cancer,
the majority of patients still do not respond to these treatments. There
is need for continued research.
==========================================================================
On April 20, 2022, researchers at the Sloan Kettering Institute reported
in the journal Nature that a recently discovered new immune cell "soldier" could be a good target for immunotherapy, raising hopes that it might
help narrow the gap between people who respond and those who do not.
The new cells, which the scientists have dubbed killer innate-like T
cells, differ in notable ways from the conventional target of many immunotherapies - - the cytotoxic (aka "killer") T cells. For one,
they don't get exhausted from extended activity like cytotoxic T cells
do. And two, they can penetrate more deeply into tissues where cancer
is hiding. These unique attributes make them attractive as a target
for immunotherapy.
"We think these killer innate-like T cells could be targeted
or genetically engineered for cancer therapy," says Ming Li, an
immunologist in SKI and the lead author of the new study. "They may be
better at reaching and killing solid tumors than conventional T cells."
Pinning Down What Makes the Cells Distinct Dr. Li's team first reported
the existence of this unusual cell population in 2016. At that time, it
was clear to his team that these cells had the power to kill cancer cells,
but they knew little about where the cells come from or how they work.
==========================================================================
For this new study, Dr. Li and colleagues used a variety of techniques, including single-cell analysis and CRISPR genome editing, to further characterize the cells.
They made several startling discoveries. For one, killer innate-like
T cells don't make the immune checkpoint molecule PD-1 and, as a
consequence, do not appear to become exhausted the way typical killer
T cells do. This is an attractive feature in a potential immune cell
therapy.
The cells also appear to recognize different markers, or antigens, on
cancer cells. Whereas conventional killer T cells recognize specific
mutated antigens (called neoantigens), the killer innate-like T cells
recognize a much broader range of non-mutated (that is, normal) antigens.
Killer innate-like T cells also don't depend on antigen-presenting
cells, such as dendritic cells, to alert them to the presence of dangerous-looking antigens. In this way, they behave more like innate
immune cells that are always primed and ready for attack.
Lastly, unlike conventional T cells, they don't recirculate throughout the blood and lymph fluid, making stops in lymph nodes. Rather, they appear to
home directly to tissues throughout the body, where they seek out danger.
==========================================================================
All of these make them of particular interest as a target of
immunotherapy, Dr.
Li says.
A Unique Fate That Avoids Autoimmunity and Suppresses Cancer The fact
that killer innate-like T cells recognize unmutated antigens in the
body raises the question of why these cells don't cause autoimmunity --
when the immune system attacks normal parts of the body. Dr. Li says
it's because they get reprogrammed during their development.
Typically, developing T cells that react strongly to normal antigens are proactively killed off by the body to prevent autoimmune reactions. But
the killer innate-like T cells escape that fate. Instead, their T cell
receptor machinery gets tamped down, rendering these cells harmless to
normal cells in the body.
At the same time, they become much more sensitive to a molecule
called IL-15 that is produced by many cancer cells and is recognized
as an "alarmin" -- a danger signal that prods the immune system into
action. The team found that if they delete IL-15 from cancer cells, then
the protection provided by the killer innate-like T cells was eliminated
and tumor growth increased.
Because IL-15 isn't highly produced in healthy tissues, the killer
innate-like T cells would not be spurred into action there, and therefore
would not cause unwanted damage.
Dr. Li's team did most of their experiments in mice, but they confirmed
that these killer innate-like T cells are present in human tumors,
including colon cancer tumors from patients at MSK. They are excited about
the possibility of working with doctors at MSK to translate these findings
from the lab to the clinic, where they might ultimately help patients.
This work was supported by the National Institute of Health (R01
CA243904-01A1, F30 AI29273-03, and F31 CA210332), the Howard Hughes
Medical Institute, the Cancer Research Institute, the Ludwig Center for
Cancer Immunotherapy and the Functional Genomic Initiative grants, and the Memorial Sloan Kettering Cancer Center (MSKCC) Support Grant/Core Grant
(P30 CA08748), the Alan and Sandra Gerry Metastasis and Tumor Ecosystems
Center of MSK.
MSK has filed a patent application regarding use of killer innate-like
T cells in cancer immunotherapy. Dr. Li is a scientific advisory board
member of and holds equity or stock options in, Amberstone Biosciences
Inc, and META Pharmaceuticals Inc.
========================================================================== Story Source: Materials provided by
Memorial_Sloan_Kettering_Cancer_Center. Note: Content may be edited for
style and length.
========================================================================== Journal Reference:
1. Chun Chou, Xian Zhang, Chirag Krishna, Briana G. Nixon, Saida Dadi,
Kristelle J. Capistrano, Emily R. Kansler, Miranda Steele, Jian Han,
Amy Shyu, Jing Zhang, Efstathios G. Stamatiades, Ming Liu, Shun Li,
Mytrang H. Do, Chaucie Edwards, Davina S. Kang, Chin-Tung Chen, Iris
H. Wei, Emmanouil P. Pappou, Martin R. Weiser, J. Garcia-Aguilar,
J. Joshua Smith, Christina S. Leslie, Ming O. Li. Programme of
self-reactive innate-like T cell-mediated cancer immunity. Nature,
2022; DOI: 10.1038/ s41586-022-04632-1 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220420133616.htm
--- up 7 weeks, 2 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)