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Published on: May 7, 2018
Mouse-Derived Gastric Organoid and Immune Cell Co-culture for the Study of the Tumor Microenvironment
Jayati Chakrabarti1, Loryn Holokai2, LiJyun Syu3
1Department of Pharmacology and System Physiology, University of Cincinnati, Cincinnati, OH, USA.
Abstract:
The interaction between the receptor, programmed cell death protein 1 (PD-1) and ligand, programmed cell death 1 (PD-L1) is known to inhibit CD8+ cytotoxic T lymphocyte proliferation, survival, and effector function. The result of this interaction leads to evasion of immune surveillance by tumors and subsequently cancer cell proliferation. Immunotherapy via PD-L1 blockade is used for a variety of malignancies, yet the prognostic value of immune checkpoint inhibition for the treatment of gastric cancer remains controversial. Thus, preclinical models that would predict the efficacy of such therapy in a subgroup of gastric cancer patients would be an advancement in the personalized treatment of this disease. Three-dimensional organoid cultures have not only been used to investigate the mechanisms regulating development and disease, but have also been used for high-throughput drug screening for targeted personalized therapy. Here we present the methodology for the co-culture of mouse-derived gastric cancer organoids with autologous immune cells specifically for the study of PD-L1/PD-1 interactions within the tumor microenvironment in vitro.
Insights
This study introduces a new method using mouse gastric cancer organoids and immune cells to study programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) interactions, aiding personalized cancer therapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- The interaction between programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) suppresses anti-tumor immune responses.
- Tumor evasion of immune surveillance through PD-1/PD-L1 signaling contributes to cancer progression.
- The efficacy of PD-L1 blockade immunotherapy in gastric cancer is not fully established, necessitating better predictive models.
Purpose of the Study:
- To develop a preclinical model for investigating PD-1/PD-L1 interactions in gastric cancer.
- To facilitate the study of immune checkpoint inhibition within the tumor microenvironment.
- To advance personalized treatment strategies for gastric cancer patients.
Main Methods:
- Co-culture of mouse-derived gastric cancer organoids with autologous immune cells.
- Establishment of a three-dimensional in vitro system.
- Focus on studying programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) interactions.
Main Results:
- A methodology for co-culturing gastric cancer organoids with immune cells is presented.
- The model allows for in vitro investigation of PD-1/PD-L1 axis in the tumor microenvironment.
- This approach supports research into immune checkpoint blockade efficacy.
Conclusions:
- The developed co-culture system provides a valuable tool for studying PD-1/PD-L1 interactions in gastric cancer.
- This model can aid in predicting patient response to immunotherapy.
- It represents a step towards personalized medicine in gastric cancer treatment.
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