We have located links that may give you full text access.
Targeted inhibition of lncRNA Malat1 alters the tumor immune microenvironment in preclinical syngeneic mouse models of triple negative breast cancer.
Cancer Immunology Research 2023 August 22
Long non-coding RNAs (lncRNA) play an important role in gene regulation in both normal tissues and cancer. Targeting lncRNAs is a promising therapeutic approach that has become feasible through the development of gapmer antisense oligonucleotides (ASOs). Metastasis-associated lung adenocarcinoma transcript (Malat1) is an abundant lncRNA whose expression is upregulated in several cancers. While Malat1 increases the migratory and invasive properties of tumor cells, its role in the tumor microenvironment (TME) is still not well defined. We explored the connection between Malat1 and the tumor immune microenvironment (TIME) using several immune competent preclinical syngeneic Tp53-null triple-negative breast cancer (TNBC) mouse models that mimic the heterogeneity and immunosuppressive TME found in human breast cancer. Using a Malat1 ASO we were able to knockdown Malat1 RNA expression resulting in a delay in primary tumor growth, decreased proliferation and increased apoptosis. Additionally, immunophenotyping of tumor-infiltrating lymphocytes (TILs) revealed that Malat1 inhibition altered the TIME, with a decrease in immunosuppressive tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) as well as an increase in cytotoxic CD8+ T cells. Malat1 depletion in tumor cells, TAMs, and MDSCs decreased immunosuppressive cytokine/chemokine secretion while Malat1 inhibition in T cells increased inflammatory secretions and T-cell proliferation. Combination of a Malat1 ASO with chemotherapy or immune checkpoint blockade (ICB) improved the treatment responses in a preclinical model. These studies highlight the immunostimulatory effects of Malat1 inhibition in TNBC, the benefit of a Malat1 ASO therapeutic, and its potential use in combination with chemotherapies and immunotherapies.
Full text links
Related Resources
Trending Papers
Guillain-Barré syndrome: History, pathogenesis, treatment, and future directions.European Journal of Neurology 2024 May 17
Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment.BMC Nephrology 2024 April 23
Angiotensin Receptor Blocker-Neprilysin Inhibitor for Heart Failure with Reduced Ejection Fraction.Pharmacological Research : the Official Journal of the Italian Pharmacological Society 2024 May 12
The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.Cardiac Failure Review 2024
European Respiratory Society Clinical Practice Guideline on symptom management for adults with serious respiratory illness.European Respiratory Journal 2024 May 9
Axillary Surgery for Breast Cancer in 2024.Cancers 2024 April 24
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app