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Tumor microenvironment (TME) plays an important role in the occurrence, progression, and therapeutic response of malignant tumor. As the main immune cells in TME, tumor-associated macrophages (TAMs) are considered to be potential key targets for cancer diagnosis and treatment. However, the functional roles and clinical significance of TAMs in colorectal cancer (CRC) remains controversial. These controversies may stem from the dynamic changes in TME and the high heterogeneity of TAMs. In this review, we systematically explore the sources, classification, identification methods and clinical significance of TAM heterogeneity in CRC. We also summarize current therapeutic approaches targeting TAMs and their limitations. In addition, differences in the function of TAMs in different stages and subtypes of CRC were analyzed, highlighting their interactions with other immune cells and signaling pathways. It suggests that developing novel therapeutic strategies based on TAM heterogeneity holds promise for advancing precision monitoring and treatment of CRC, and promote the further development of tumor immunotherapy.
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http://dx.doi.org/10.1016/j.prp.2025.156082 | DOI Listing |
FASEB J
September 2025
Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Tumor-associated macrophages (TAMs) act as a vital player in the immunosuppressive tumor microenvironment (TME) and have received widespread attention in the treatment of cancer in recent times. Nevertheless, simultaneously inducing TAM repolarization and strengthening their phagocytic ability on cancer cells is still a significant challenge. Ferroptosis has received widespread attention due to its lethal effects on tumor cells, but its role in TAMs and its impact on tumor progression have not yet been defined.
View Article and Find Full Text PDFCancer Immunol Res
September 2025
The Wistar Institute, Philadelphia, PA, United States.
Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by immunosuppressive tumor microenvironment (TME) maintained by tumor-associated macrophages (TAMs) hindering anti-tumor responses and immunotherapy efficacy. Here we show that targeting retinoblastoma protein (Rb) by disruption of its LxCxE cleft pocket causes preferential cell death in Rbhigh M2 polarized or M2-like Rbhigh immunosuppressive TAMs by induction of ER stress, p53 and mitochondria-related cell death pathways.
View Article and Find Full Text PDFJ Inflamm Res
September 2025
Department of the Head and Neck, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, People's Republic of China.
Background: Immune escape of tumor cells is a common problem with tumor photothermal therapy utilizing gold nanorods (Au NRs). Whether CpG ODN, an immune adjuvant, can synergize with Au NRs to activate the immune response and its potential mechanism is not clear.
Methods: The effect of Au NRs combined with CpG ODN (Au NRs-C) on the activity of various immune-related cells, such as double-positive T cells, macrophages, NK cells, Th17, and Treg.
Adv Pharm Bull
July 2025
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Purpose: The survival and progression of multiple myeloma (MM) cells rely heavily on supportive factors and cells within the MM microenvironment, notably macrophages. The PI3K signaling pathway plays a crucial role in both myeloma cells survival and macrophage polarity, making it a potential target for altering the MM microenvironment dynamics.
Methods: In this study, the impact of LY294002, a PI3K signaling pathway inhibitor, on the viability of U266 myeloma cells in mono-culture and MM patient-derived bone marrow mononuclear cells (BM-MNCs) in co-culture was investigated.
Cell Signal
September 2025
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Respiratory Immunology research center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. 2.48 million new cases were reported globally in 2022, driven by rising adenocarcinoma rates linked to environmental factors such as air pollution.
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