Researchers identify molecule that blocks immune cells from entering and killing breast tumors
Study reveals new way to infiltrate hard-to-treat cancers, unlocking key
to potential therapeutic agents

Date:
November 3, 2021
Source:
George Washington University
Summary:
Researchers have identified a key molecule in certain kinds of
breast cancers that prevent immune cells from entering tumors
and killing the cancer cells inside. This research could pave
the way toward a new treatment for certain kinds of aggressive
breast cancer.



FULL STORY ========================================================================== George Washington University researchers have identified a key molecule in certain kinds of breast cancers that prevent immune cells from entering
tumors and killing the cancer cells inside. The paper and its findings, published today in Nature, could pave the way toward a new treatment
for certain kinds of aggressive breast cancer.


========================================================================== "During cancer progression, this molecule, known as DDR1, organizes a
high- order extracellular matrix that acts like barbed wire around the
boundary of a tumor to prevent immune cells from entering the tumor,"
Rong Li, the Ross Professor of Basic Science Research at GW and lead
author of the paper, said.

"Knowing that the DDR1 molecule creates a protective boundary around
tumors, we were able to use pre-clinical models to show that the moment
you deactivate DDR1, immune cells can infiltrate the tumor and kill the
cells inside." Li and his colleagues studied triple-negative breast
cancer, an aggressive form of cancer that accounts for about 15% of
all breast cancer cases. This type of cancer, according to the Centers
for Disease Control and Prevention, lacks the receptors commonly used
in targeted cancer therapies, making it difficult to target the tumor
cells. Immunotherapy is designed to activate immune cells when they can
get to the center of a tumor, but the DDR1 molecule puts up a physical
barrier to anti-tumor immune cells. Identifying the underlying mechanism
could provide a new way of looking for novel therapeutic agents for this hard-to- treat cancer, Li said.

In the Nature study, the researchers assessed the impact of removing
DDR1 in multiple pre-clinical models. They determined that knocking out
DDR1 not only halts tumor growth, but it also may protect the body from
future tumors.

In conjunction with the new findings, co-corresponding author Zhiqiang
An has developed a therapeutic DDR1-targeting antibody that breaks down
that line of defense and helps tumor-killing immune cells cross.

"The discovery of the important role of DDR1 in cancer resistance is a significant advance that can potentially transform treatment pathways,"
said An, who serves as director of the Texas Therapeutics Institute and a professor of molecular medicine at The University of Texas Health Science Center at Houston (UTHealth Houston). "I'm delighted by the collaboration between researchers and academic labs, excited by synergies of basic and translational research, and encouraged by the rapid translation from
discovery to therapeutic candidates for the benefit of people living
with cancer." With this more comprehensive understanding of DDR1,
researchers also hope to identify additional molecules like DDR1 and
use the same approach to fight other cancers.

========================================================================== Story Source: Materials provided by George_Washington_University. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiujie Sun, Bogang Wu, Huai-Chin Chiang, Hui Deng, Xiaowen Zhang,
Wei
Xiong, Junquan Liu, Aaron M. Rozeboom, Brent T. Harris, Eline
Blommaert, Antonio Gomez, Roderic Espin Garcia, Yufan Zhou, Payal
Mitra, Madeleine Prevost, Deyi Zhang, Debarati Banik, Claudine
Isaacs, Deborah Berry, Catherine Lai, Krysta Chaldekas, Patricia
S. Latham, Christine A.

Brantner, Anastas Popratiloff, Victor X. Jin, Ningyan Zhang,
Yanfen Hu, Miguel Angel Pujana, Tyler J. Curiel, Zhiqiang An, Rong
Li. Tumour DDR1 promotes collagen fibre alignment to instigate
immune exclusion. Nature, 2021; DOI: 10.1038/s41586-021-04057-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211103140052.htm

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