Wira Eka Putra, Adawiyah Suriza Shuib, Nurhanan Murni Yunos
With rapid progress in tumor immunology, the complexity and impact of the tumor microenvironment (TME) in cancer con-tinue to grow. As a major component of TME, tumor-associated macrophages (TAMs) play a pivotal role in cancer progression by promoting angiogenesis, metastasis, and therapy resistance. TAMs contribute to an immunosuppressive environment by secreting cytokines and factors that inhibit anti-tumor immunity. Therefore, targeting TAMs, particularly by promoting their repolarization into M1-like phenotypes, has emerged as a key strategy in cancer treatment. Plant-derived natural products, well-known for their therapeutic potential against various ailments, including cancer, are gaining interest for their ability to modulate TAMs. Leveraging these natural products could provide opportunities to optimize cancer therapy, particularly by targeting TAMs to overcome immunosuppressive barriers. This paper focuses on the components of TME, with a specific emphasis on the biological aspects of TAMs and the impact of natural products on TAMs across various cancer cases. Furthermore, we outline the mechanisms and anti-tumor effects of selected compounds, especially their ability to promote TAM repolarization toward M1-like phenotypes, providing new insights and potential therapeutic options for cancer treatment. © 2026, Romanian Society for Pharmaceutical Sciences. All rights reserved.
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; Biotechnology Study Program, Department of Applied Sciences, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, East Java, 65145, Indonesia; Natural Products Division, Forest Research Institute Malaysia (FRIM), Selangor, Kepong, 52109, Malaysia
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