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Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and
Qingman He1, Li Xiang1, Yuanyuan Luo1
1Department of Rheumatology and Immunology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Abstract:
Colon cancer persists as a major global health burden due to therapy resistance and metastasis, with tumor-associated macrophages (TAMs) in the microenvironment driving progression through immune evasion and angiogenesis. This review highlights plant-derived therapeutics targeting TAMs to disrupt protumor signaling. Key phytochemicals (e.g., Curcumin, Cucurbitacin B, Astragaloside IV) suppress M2 polarization via NF-κB/STAT3 inhibition, block VEGF/HIF-1α-mediated angiogenesis, and enhance antitumor immunity by downregulating PD-L1. Cannabidiol, Hydroxygenkwanin regulate TAM metabolism. Dietary agents like sulforaphane and β-glucans modulate TAM-gut microbiome crosstalk. Nanoparticle-encapsulated phytochemicals enhance TAM-targeted delivery, while clinical translation requires standardized phytopreparations and biomarker-guided trials. We propose integrating validated botanical adjuvants (e.g., Fucoidan for TLR4 inhibition, dihydroisotanshinone I for CCL2 suppression) with immunotherapies to remodel immunosuppressive niches. Phytotherapy offers a multifaceted strategy to overcome TAM-driven therapeutic barriers in colon cancer, emphasizing plant-based precision medicine to augment conventional treatments.
Insights
Plant compounds can target tumor-associated macrophages (TAMs) to combat colon cancer progression. This approach offers a natural strategy to enhance conventional therapies by overcoming treatment resistance.
Area of Science:
- Oncology
- Immunology
- Pharmacology
- Natural Product Chemistry
Background:
- Colon cancer remains a significant global health challenge, characterized by therapy resistance and metastasis.
- Tumor-associated macrophages (TAMs) within the tumor microenvironment promote cancer progression via immune evasion and angiogenesis.
- Targeting TAMs presents a promising strategy to overcome therapeutic barriers in colon cancer treatment.
Purpose of the Study:
- To review plant-derived therapeutics that target TAMs to disrupt protumor signaling pathways in colon cancer.
- To explore the potential of phytochemicals and botanical agents as adjuncts to conventional cancer therapies.
- To highlight strategies for enhancing the delivery and clinical translation of plant-based colon cancer treatments.
Main Methods:
- Literature review of studies investigating plant-derived compounds and their effects on TAMs.
- Analysis of phytochemical mechanisms, including suppression of M2 polarization, inhibition of angiogenesis, and modulation of immune responses.
- Evaluation of nanoparticle delivery systems and potential clinical translation strategies for botanical adjuvants.
Main Results:
- Key phytochemicals (Curcumin, Cucurbitacin B, Astragaloside IV) suppress M2 TAM polarization via NF-κB/STAT3 inhibition.
- Plant compounds inhibit VEGF/HIF-1α-mediated angiogenesis and enhance antitumor immunity by downregulating PD-L1.
- Dietary agents (sulforaphane, β-glucans) modulate TAM-gut microbiome interactions; nanoparticle encapsulation improves delivery.
Conclusions:
- Phytotherapy offers a multifaceted strategy to overcome TAM-driven therapeutic resistance in colon cancer.
- Botanical adjuvants like Fucoidan and dihydroisotanshinone I can remodel immunosuppressive tumor microenvironments.
- Integrating validated plant-based agents with conventional treatments represents a promising avenue for plant-based precision medicine in oncology.
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