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Published on: August 25, 2023
Genetic screens to study the immune system in cancer
Kai W Wucherpfennig1, Adam Nr Cartwright2
1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
RNA interference and CRISPR/Cas9 technologies now enable systematic discovery of genes that regulate key pathways in the complex interaction between immune cells and tumor cells. Discovery screens are feasible in an in vivo setting, allowing identification of genes that limit the effectiveness of anti-tumor immunity. In vivo discovery screens can be informed by single-cell RNA-seq experiments that define the differentially expressed genes between functionally distinct immune cell subpopulations, both in humans and relevant animal models. Novel targets for cancer immunotherapy are being defined by the in depth functional annotation of immunosuppressive pathways in the tumor microenvironment.
Insights
New gene discovery tools like RNA interference and CRISPR/Cas9 help identify genes limiting anti-tumor immunity. This research uses in vivo screens and single-cell RNA-seq to find novel cancer immunotherapy targets.
Area of Science:
- Immunology
- Genetics
- Cancer Research
Background:
- The interaction between immune and tumor cells is complex and involves numerous regulatory pathways.
- Identifying genes that suppress anti-tumor immunity is crucial for developing effective cancer therapies.
Purpose of the Study:
- To systematically discover genes regulating the immune-tumor cell interaction.
- To identify novel targets for cancer immunotherapy by analyzing immunosuppressive pathways in the tumor microenvironment.
Main Methods:
- Utilizing RNA interference and CRISPR/Cas9 technologies for gene discovery.
- Performing in vivo discovery screens to identify genes limiting anti-tumor immunity.
- Employing single-cell RNA-sequencing (scRNA-seq) to analyze gene expression in immune cell subpopulations.
Main Results:
- Systematic discovery of genes involved in immune-tumor cell interactions is now feasible.
- In vivo screens can identify genes that hinder anti-tumor immune responses.
- scRNA-seq provides insights into differentially expressed genes in distinct immune cell types.
Conclusions:
- Novel targets for cancer immunotherapy can be identified through functional annotation of immunosuppressive pathways.
- Advanced genetic tools and single-cell analysis are powerful approaches for understanding tumor immunology.
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