Progress in tumor-associated macrophage (TAM)-targeted therapeutics.

Adv Drug Deliv Rev

Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, United States. Electronic address:

Published: May 2017

As an essential innate immune population for maintaining body homeostasis and warding off foreign pathogens, macrophages display high plasticity and perform diverse supportive functions specialized to different tissue compartments. Consequently, aberrance in macrophage functions contributes substantially to progression of several diseases including cancer, fibrosis, and diabetes. In the context of cancer, tumor-associated macrophages (TAMs) in tumor microenvironment (TME) typically promote cancer cell proliferation, immunosuppression, and angiogenesis in support of tumor growth and metastasis. Oftentimes, the abundance of TAMs in tumor is correlated with poor disease prognosis. Hence, significant attention has been drawn towards development of cancer immunotherapies targeting these TAMs; either depleting them from tumor, blocking their pro-tumoral functions, or restoring their immunostimulatory/tumoricidal properties. This review aims to introduce readers to various aspects in development and evaluation of TAM-targeted therapeutics in pre-clinical and clinical stages.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581987PMC
http://dx.doi.org/10.1016/j.addr.2017.04.010DOI Listing

Publication Analysis

Top Keywords

tam-targeted therapeutics
8
tams tumor
8
progress tumor-associated
4
tumor-associated macrophage
4
macrophage tam-targeted
4
therapeutics essential
4
essential innate
4
innate immune
4
immune population
4
population maintaining
4

Similar Publications

Tumor-associated macrophages (TAMs) undergo metabolic reprogramming, encompassing glucose, amino acid, fatty acid metabolism, tricarboxylic acid (TCA) cycle, purine metabolism, and autophagy, within the tumor microenvironment (TME). The metabolic interdependencies between TAMs and tumor cells critically influence macrophage recruitment, differentiation, M2 polarization, and secretion of epithelial-mesenchymal transition (EMT)-related factors, thereby activating intratumoral EMT pathways and enhancing tumor cell invasion and metastasis. Tumor cell metabolic alterations, including hypoxia, metabolite secretion, aerobic metabolism, and autophagy, affect the TME's metabolic landscape, driving macrophage recruitment, differentiation, M2 polarization, and metabolic reprogramming, ultimately facilitating EMT, invasion, and metastasis.

View Article and Find Full Text PDF

Tumor-associated macrophages (TAMs) greatly contribute to immune checkpoint inhibitor (ICI) resistance of cancer. However, its underlying mechanisms and whether TAMs can be promising targets to overcome ICI resistance remain to be unveiled. Through integrative analysis of immune multiomics data and single-cell RNA-seq data (iMOS) in lung adenocarcinoma (LUAD), lymphotoxin β receptor () is identified as a potential immune checkpoint of TAMs, whose high expression, duplication, and low methylation are correlated with unfavorable prognosis.

View Article and Find Full Text PDF

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth.

View Article and Find Full Text PDF

Targeted reprogramming of tumor-associated macrophages for overcoming glioblastoma resistance to chemotherapy and immunotherapy.

Biomaterials

December 2024

School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, China. Electronic address:

The resistance of glioblastoma multiforme (GBM) to standard chemotherapy is primarily attributed to the existence of tumor-associated macrophages (TAMs) in the GBM microenvironment, particularly the anti-inflammatory M2 phenotype. Targeted modulation of M2-TAMs is emerging as a promising strategy to enhance chemotherapeutic efficacy. However, combination TAM-targeted therapy with chemotherapy faces substantial challenges, notably in terms of delivery efficiency and targeting specificity.

View Article and Find Full Text PDF

The Role of TAMs in the Regulation of Tumor Cell Resistance to Chemotherapy.

Crit Rev Oncog

July 2024

Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine at UCLA, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA.

Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in the immunosuppressive tumor microenvironment (TME). TAMs are central to fostering pro-inflammatory conditions, tumor growth, metastasis, and inhibiting therapy responses. Many cancer patients are innately refractory to chemotherapy and or develop resistance following initial treatments.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!