Unlocking Gut Microbiome-Immunity Synergy: ANT BIO PTE. LTD. Products Empower Flaxseed Lignans Combined with PD-1 Inhibitor for Breast Cancer Therapy

1. Literature Information

Title: The combination of flaxseed lignans and PD-1/PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity

Journal: Drug Resistance Updates (Impact Factor: 21.7)

DOI: https://doi.org/10.1016/j.drup.2025.101222

Core Reagents from ANT BIO PTE. LTD.: 5-Color Multiplex Immunofluorescence IHC Staining Kit (Catalog No.: abs50029), Rabbit anti-CD38 Polyclonal Antibody (Catalog No.: abs136071)

2. Research Background and Core Ideas: Targeting the Pain Point of "Immunotherapy Resistance", Exploring the Synergistic Value of Natural Products and Microbiota

2.1 Clinical Pain Point: Limited Efficacy of PD-1 Inhibitor Monotherapy

Current PD-1/PD-L1 inhibitors (PDi) have a low response rate in breast cancer patients, and most patients face drug resistance or recurrence. There is an urgent need to find combined partners that can "activate immunity and reverse drug resistance".

2.2 Research Hypothesis: Flaxseed Lignans (FL) May Be an Ideal Partner

FL is a natural compound rich in flaxseed lignans (mainly composed of SDG) and has been proven to have anti-cancer activity. The research team hypothesized that FL may enhance the anti-breast cancer effect of PDi by regulating the gut microbiome (known to affect the efficacy of immunotherapy) or host immunity.

2.3 Core Research Ideas (Three-Step Mechanism Verification)

•         ① Step 1: Verify the anti-breast cancer activity of FL — In vitro and in vivo experiments to clarify whether FL inhibits breast cancer growth and whether it is dependent on the gut microbiome;

•         ② Step 2: Explore the core mechanism of action — Identify key metabolites of FL (such as ENL) and downstream targets (such as CD38), and clarify the role of the "FL→gut microbiome→ENL→CD38" axis;

•         ③ Step 3: Verify the combined efficacy — Detect the anti-tumor effect of FL combined with PDi (BMS-1), and analyze changes in the gut microbiome (such as Akkermansia) and tumor immune microenvironment (TIM).

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3. Key Research Results: FL + PD-1 Inhibitor "Dual Pronged Approach", Gut Microbiome + Immunity Synergistically Against Tumors

Through in vitro and in vivo experiments, the research team confirmed the core value of FL in breast cancer treatment. The following are the three major key breakthroughs:

3.1 FL Inhibits Breast Cancer Progression Through the "Gut Microbiome→ENL→CD38" Axis

Core Finding: FL needs to be converted into the metabolite enterolactone (ENL) by the gut microbiome to significantly downregulate CD38 (a key gene related to immunosuppression and PDi resistance), thereby inhibiting the proliferation, migration and invasion of breast cancer cells (such as 4T1 and BT549 cells).

In Vivo Verification: After oral administration of FL to breast cancer mice, the tumor volume and weight were significantly reduced; if antibiotics were used to destroy the gut microbiome, the anti-tumor effect of FL was greatly weakened; supplementing ENL or fecal microbiota transplantation (FMT) from FL-treated mice could restore the anti-tumor activity.

Mechanism Evidence: After overexpression of CD38, the inhibitory effect of ENL on breast cancer cells was "offset", and the anti-tumor effect of FL alone disappeared, confirming that CD38 is a key target for FL/ENL to exert their effects.

3.2 FL Significantly Enhances the Anti-Tumor Effect of PD-1 Inhibitors

Combination Advantage: Compared with single drugs (FL or BMS-1), the combination of FL and PD-1 inhibitor (BMS-1) (FLcPDi group) could more significantly reduce the tumor volume and weight of mice without increasing abnormal body weight (excluding toxicity).

Molecular Evidence: IHC detection showed that the expression of CD38 in the tumors of mice in the FL or FLcPDi group was significantly downregulated, further verifying the mechanism that "FL enhances PDi efficacy by downregulating CD38".

3.3 FL Regulates Gut Microbiome and Tumor Immune Microenvironment (TIM), Remodeling Anti-Tumor Immunity

Gut Microbiome Changes: 16S rDNA sequencing showed that FLcPDi treatment significantly increased the abundance of Akkermansia in the intestines of mice; supplementing Akkermansia could restore the sensitivity of antibiotic-treated mice to PDi, confirming that it is a key microbiome for FL to enhance immunotherapy.

TIM Optimization: Multiplex immunohistochemistry (mIHC) detection found that FL treatment could significantly increase the infiltration of CD3+, CD4+, CD8+ immune cells in the tumor and reduce immunosuppressive F4/80+ macrophages; CyTOF further confirmed that the proportion of memory CD4+ T and memory CD8+ T cells in the FLcPDi group increased, while the proportion of M2 macrophages decreased, significantly improving the immunosuppressive microenvironment.

4. ANT BIO PTE. LTD. Products: Precise Detection Tools to Support Mechanism Verification and Result Output

The core data of this study (such as TIM immune cell analysis and CD38 expression verification) all relied on high-specificity reagents from ANT BIO PTE. LTD. The two key products directly supported the key links of mechanism exploration:

4.1 5-Color Multiplex Immunofluorescence IHC Staining Kit (Anti-Rabbit Secondary Antibody) (Catalog No.: abs50029–100T)

Application Scenario: Multiplex immunohistochemistry (mIHC) detection of tumor tissues

Research Role: Simultaneously label CD3+ (orange), CD4+ (yellow), CD8+ (pink), and F4/80+ (red) cells in the tumor microenvironment, realizing "detection of multiple immune cells on one section", and accurately quantifying the changes in the cellular composition of TIM after FL treatment.

Product Advantages: Stable fluorescent signals and high specificity, avoiding the low efficiency problem of traditional IHC "only detecting one target at a time", and providing an efficient tool for complex microenvironment analysis.

4.2 CD38-Specific Antibody (Catalog No.: abs136071)

Application Scenario: Immunohistochemistry (IHC) detection of tumor tissues

Research Role: Detect the expression level of CD38 protein in mouse tumors of different treatment groups (control group, FL group, BMS-1 group, FLcPDi group), verify the core mechanism of "FL/ENL downregulating CD38", and the effect of combined PDi on CD38 expression.

Results Showed: The CD38 positive signal in the tumors of the FL or FLcPDi group was significantly weaker than that of the control group, directly proving that FL can enhance PDi efficacy by downregulating CD38, and providing key morphological evidence for the "FL/ENL/CD38 axis".

Product Advantages: High antibody affinity and low background signal, which can accurately capture the expression difference of CD38 in tumor tissues, providing reliable IHC data for mechanism verification.

5. Brand Mission

As a professional supplier of life science reagents, ANT BIO PTE. LTD. is dedicated to providing high-quality, reliable products and comprehensive solutions to empower global life science research. The company's three specialized sub-brands—Absin focusing on general reagents and kits, Starter on antibodies, and UA on recombinant proteins—cover the full spectrum of research needs in the life science field. Our core mission is to bridge the gap between cutting-edge scientific research and practical applications, accelerate the pace of scientific discovery, and contribute to the advancement of human health and regenerative medicine.

6. Related Product List

Products Used in This Study

More Multiplex Immunofluorescence IHC Kits

7. Disclaimer

This article is AI-compiled and interpreted based on the original work in DOI: 10.1002/advs.202413562. All intellectual property (e.g., images, data) of the original publication shall belong to the journal and the research team. For any infringement, please contact us promptly and we will take immediate action.

8. Brand Promotion Copy

ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.