The tumor microenvironment (TME) influences tumor growth, metastatic spread and response to treatment. Often immunosuppression, mediated by the TME, impairs a beneficial response. The complexity of the tumor composition challenges our abilities to design new and more effective therapies. Going forward we will need to 'manage' the content and or functionality of the TME to improve treatment outcomes. Currently, several different kinds of treatments are available to patients with cancer: there are the traditional approaches of chemotherapy, radiation and surgery; there are targeted agents that inhibit kinases associated with oncogenic pathways; there are monoclonal antibodies that target surface antigens often delivering toxic payloads or cells and finally there are antibodies and biologics that seek to overcome the immunosuppression caused by elements within the TME. How each of these therapies interact with the TME is currently under intense and widespread investigation. In this review we describe how the TME and its immunosuppressive components can influence both tumor progression and response to treatment focusing on three particular tumor types, classic Hodgkin Lymphoma (cHL), Pancreatic Ductal Adenocarcinoma (PDAC) and Glioblastoma Multiforme (GBM). And, finally, we offer five approaches to manipulate or manage the TME to improve outcomes for cancer patients.
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http://dx.doi.org/10.3389/fimmu.2022.954992 | DOI Listing |
J Transl Med
January 2025
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Background: The progression of bladder cancer (BC) from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) significantly increases disease severity. Although the tumor microenvironment (TME) plays a pivotal role in this process, the heterogeneity of tumor cells and TME components remains underexplored.
Methods: We characterized the transcriptomes of single cells from 11 BC samples, including 4 NMIBC, 4 MIBC, and 3 adjacent normal tissues.
ACS Biomater Sci Eng
January 2025
Changchun University of Science and Technology, Changchun 130022, Jilin, China.
The cancer-associated fibroblasts (CAFs) in tumor stroma present substantial barriers to drug penetration, resulting in tumor resistance and progression. One promising strategy is to reprogram CAFs into a quiescent state, which necessitates novel approaches. Our study introduces a sequential treatment strategy using chitosan thermosensitive hydrogels loaded with α-Mangostin (α-M), a small molecule drug with antifibrotic properties, aimed at reprogramming CAFs within the breast cancer tumor microenvironment (TME).
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Second Department of Cardiovascular Medicine, Shengjing Hospital Affiliated to China Medical University, No. 36, Sanhao Street, Heping District, Shenyang 110004, Liaoning Province, China. Electronic address:
This work optimized proteoglycan-degrading enzymes through targeted mutagenesis to enhance their interaction with the tumor microenvironment in Renal Cell Carcinoma (RCC). A comprehensive mutagenesis approach identified 60 key mutations significantly improving enzymatic activity, stability, and structural integrity. When compared to Wild Type (WT) enzyme, a remarkable increase in specific activity by 35 % (p < 0.
View Article and Find Full Text PDFPharmacol Res
January 2025
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address:
Gastric cancer remains a significant global health burden, characterized by regional variations in incidence and poor survival prospects in advanced stages. Natural killer (NK) cells play a crucial role in the body's anti-cancer defense, and chimeric antigen receptor (CAR)-NK cell therapy is gaining attention as a cutting-edge and promising treatment method. This study aims to tackle the challenge of TGF-β-mediated tumor immune evasion within the immunosuppressive tumor microenvironment by designing a novel chimeric cytokine receptor TRII/21R, which consists of extracellular domains of TGF-β receptor II (TRII) and transmembrane and intracellular domains of IL-21 receptor (21R) and can convert the immunosuppressive signal from TGF-β in the tumor microenvironment (TME) into an NK cell activation signal through the IL-21R-STAT3 pathway.
View Article and Find Full Text PDFJ Drug Target
January 2025
Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar, India.
Endoplasmic Reticulum (ER) stress is intricately involved in cancer development, progression and response to chemotherapy. ER stress related genes might play an important role in predicting the prognosis in lung adenocarcinoma patients and may be manipulated to improve the treatment outcome and overall survival rate. In this review, we analyzed the contribution of the three major ER stress pathways-IRE1, ATF6, and PERK-in lung cancer pathogenesis via modulation of tumor microenvironment (TME) and processes as metastasis, angiogenesis, apoptosis and N-glycosylation.
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