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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Probiotics01:22

Probiotics

Probiotics are live, non-pathogenic microorganisms that confer health benefits by modulating the gut microbiota. The human gastrointestinal tract harbors a complex microbial ecosystem, and the balance of this microbiota is crucial for digestive and systemic health. Among the most extensively studied and utilized probiotics are species formerly classified within the genera Lactobacillus and Bifidobacterium. These organisms not only naturally colonize the human gut but are also consumed through...

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Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
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Lactate-Depleting Engineered Probiotics Remodel the Tumor Microenvironment and Enhance PD-1 Blockade.

Jing Zhang1, Qiushuang Zhang2, Yuhan Liu2

  • 1Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, China.

Advanced Healthcare Materials
|June 2, 2026
PubMed
Summary

Engineered probiotics like Lac-EcN consume tumor lactate, boosting anti-tumor immunity. Combining this with anti-PD-1 therapy enhances cancer treatment and survival in preclinical models.

Keywords:
cancer immunotherapyengineered probioticslactate metabolism, PD‐1 blockadetumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Microbiology

Background:

  • High lactate levels in the tumor microenvironment (TME) inhibit anti-tumor immune responses.
  • Targeted strategies to reduce intratumoral lactate are needed for effective cancer therapy.

Purpose of the Study:

  • To develop an engineered probiotic (Lac-EcN) for targeted lactate consumption within the TME.
  • To evaluate the efficacy of Lac-EcN in modulating the TME and enhancing anti-tumor immunity.

Main Methods:

  • Development of an engineered probiotic, Lac-EcN, for lactate consumption.
  • Administration of Lac-EcN in B16-F10 melanoma and MC-38 colorectal carcinoma models.
  • Assessment of intratumoral lactate levels, tumor acidosis, Treg function, and cytotoxic T cell activity.
  • Combination therapy with Lac-EcN and anti-PD-1 immune checkpoint blockade.

Main Results:

  • Lac-EcN significantly reduced intratumoral lactate by over 60% and alleviated tumor acidosis.
  • Treatment reversed aberrant NFAT1 nuclear translocation in Tregs and restored effector molecule production in cytotoxic T cells.
  • Combination of Lac-EcN and anti-PD-1 improved tumor inhibition and extended survival in preclinical cancer models.

Conclusions:

  • Engineered probiotics represent a viable platform for targeted metabolic interventions within the TME.
  • Metabolic reprogramming via Lac-EcN can be integrated with immune checkpoint blockade for enhanced cancer immunotherapy.
  • This approach offers a novel strategy for overcoming lactate-mediated immunosuppression in cancer.