Research team shares new data on how XPO1 blockade may boost
immune-based treatments: •New preclinical findings reported in
Cellular & Molecular Immunology •XPO1 plays key role in MDSC
differentiation, resulting in tumor progression •Team sees possible
application for FDA-approved drug selinexor in solid tumors
BUFFALO,
N.Y., June 20, 2024 /PRNewswire-PRWeb/ -- A
team of Roswell Park Comprehensive Cancer Center experts led by
Hemn Mohammadpour, DVM, PhD, conducted research that offers new
insights into tumor biology and may lay the groundwork for more
effective cancer immunotherapy. Their preclinical findings were
published today in the journal Cellular & Molecular
Immunology.
"The potential benefit of combining XPO1
blockade with existing and future immunotherapies holds promise for
improving patient outcomes while also expanding the arsenal of
available treatment options for patients with various cancer
types."
"We discovered that a protein highly expressed by tumor cells
and targeted in treatments for cancers like multiple myeloma is
also highly expressed by myeloid-derived suppressor cells," notes
Saeed Daneshmandi, PhD, study first
author and a postdoctoral researcher with the Department of Cell
Stress Biology at Roswell Park. "This discovery is important
because it reveals the previously unknown immunoregulatory
mechanism of the FDA-approved Exportin 1 inhibitor selinexor,
suggesting that XPO1 blockade could be effective in combination
therapy — particularly in solid tumors, where selinexor alone has
shown limited success."
Myeloid-derived suppressor cells (MDSCs) are known to promote
tumor progression through the suppression of the body's antitumor
immune response. Gaining further understanding into the mechanisms
that govern their development and immunosuppressive functions could
reveal new therapeutic targets to improve antitumor immunity.
Exportin 1 (XPO1), a nuclear export protein, plays an essential
part in the transport of many proteins and RNA molecules from the
nucleus to the cytoplasm. Overexpression of XPO1 is common in many
cancer types, including multiple myeloma, pancreatic, ovarian,
glioma, lung, stomach, prostate and colorectal tumors, and is
associated with poor prognosis.
In a prior exploratory single-cell RNA sequencing study
exploring MDSC heterogeneity, Dr. Mohammadpour and colleagues
uncovered the potential importance of XPO1 for myeloid-derived
suppressor cell differentiation and function.
Despite extensive knowledge regarding XPO1's role in cancer
cells, its function in myeloid cells, particularly myeloid-derived
suppressor cells, remains largely unexplored. Dr. Mohammadpour and
colleagues aimed to investigate XPO1's impact on MDSC
differentiation and immunosuppressive functions, as well as to
understand the mechanisms by which XPO1 regulates these properties
in MDSCs.
"Our findings revealed that selinexor, an FDA-approved XPO1
inhibitor, reduces tumor progression partly by blocking MDSCs,
inducing neutrophil-like cells with antitumor capabilities, and
enhancing the antitumor immune response," says Dr. Mohammadpour.
"This discovery is significant because it suggests that selinexor
could be used as an immunomodulatory agent to improve the
effectiveness of standard treatments, such as immune checkpoint
inhibition."
"The potential benefit of combining XPO1 blockade with existing
and future immunotherapies holds promise for improving patient
outcomes while also expanding the arsenal of available treatment
options for patients with various cancer types," Dr. Mohammadpour
says.
This study was supported by funds provided by the National Heart
Lung Blood Institute (grants K99HL155792, R00HL155792), the
National Cancer Institute (grant R01CA205246) and the Roswell Park
Alliance Foundation, including a donation from Brendan and Elise McCarthy.
From the world's first chemotherapy research to the PSA prostate
cancer biomarker, Roswell Park Comprehensive Cancer Center
generates innovations that shape how cancer is detected, treated
and prevented worldwide. Driven to eliminate cancer's grip on
humanity, the Roswell Park team of 4,000 makes compassionate,
patient-centered cancer care and services accessible across
New York State and beyond. Founded
in 1898, Roswell Park was among the first three cancer centers
nationwide to become a National Cancer Institute-designated
comprehensive cancer center and is the only one to hold this
designation in Upstate New York. To learn more about Roswell Park
Comprehensive Cancer Center and the Roswell Park Care Network,
visit http://www.roswellpark.org, call 1-800-ROSWELL
(1-800-767-9355) or email ASKRoswell@RoswellPark.org.
Media Contact
Annie Deck-Miller, Roswell Park
Comprehensive Cancer Center, 716-845-8593,
ann.deck-miller@roswellpark.org, roswellpark.org
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SOURCE Roswell Park Comprehensive Cancer Center