This technology employs CRISPR-mediated inactivation of the MLH1 gene within CT26 and MC-38 murine colorectal tumor cell lines to simulate DNA mismatch repair deficiency, resulting in microsatellite instability. It enables the creation of isogenic models that allow researchers to directly compare tumor behavior in both immuno-compromised and immuno-competent environments. The modified cells exhibit distinct growth patterns, apoptotic activity, and cytokine expression, as well as increased CD8+ T cell infiltration, providing a comprehensive platform to study how DNA repair defects can influence tumor dynamics and immune interactions.
Description
What differentiates this approach is its capacity to link programmed cell death with subsequent immune responses. By demonstrating that caspase inhibition suppresses both cytokine induction and T cell infiltration, the system reveals a crucial mechanistic role of apoptosis in triggering antitumor immunity. This insight not only deepens our understanding of how microsatellite instability affects tumor pathology but also highlights the therapeutic potential for leveraging cellular death mechanisms to enhance the efficacy of immune-based cancer treatments.
Applications
- Immunotherapy drug screening
- Preclinical model testing
- Colorectal cancer therapy development
- Cell line licensing
Advantages
- Enables the creation of isogenic tumor models to study differences between immuno-compromised and immuno-competent environments.
- Provides mechanistic insights into how DNA mismatch repair deficiency leads to microsatellite instability and influences tumor growth.
- Demonstrates the role of caspase-mediated apoptosis in triggering inflammatory cytokine production and CD8+ T cell infiltration.
- Offers a valuable tool for developing and testing new immunotherapies for colorectal cancer patients with deficient mismatch repair.
- Facilitates direct comparison of tumor behavior, enhancing our understanding of antitumor immune responses.
IP Status
Research Tool
