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The (re)discovery of tumor-intrinsic determinants of immune sensitivity by functional genetic screens
D W Vredevoogd1, G Apriamashvili1, D S Peeper1
1Netherlands Cancer Institute, Oncode Institute, Division of Molecular Oncology and Immunology, Amsterdam, The Netherlands.
Abstract:
Functional genetic screens by CRISPR-Cas9 allow for the unbiased discovery of proteins causally involved in complex biological processes. In recent years, this approach has been used by multiple laboratories to uncover a range of tumor cell regulators determining immune sensitivity. In this review, we provide an overview of genetic screens carried out both in vitro and in vivo. By comparative analysis we highlight commonly identified proteins and pathways that are key in establishing tumor-intrinsic immune susceptibility. Together, these screens demonstrated the importance of the antigen presentation, interferon-γ, tumor necrosis factor and autophagy pathways in governing sensitivity of tumor cells to immune attack. Moreover, they underline the complex interplay between tumor cells and their microenvironment, providing both fundamental and clinically relevant insights into the mechanisms of tumor immune resistance.
Insights
CRISPR-Cas9 genetic screens reveal key proteins and pathways regulating tumor cell immune sensitivity. These findings illuminate tumor-intrinsic immune susceptibility and resistance mechanisms for clinical relevance.
Area of Science:
- Genomics
- Immunology
- Cancer Biology
Background:
- CRISPR-Cas9 functional genetic screens offer unbiased discovery of proteins in biological processes.
- These screens have identified tumor cell regulators impacting immune sensitivity.
Purpose of the Study:
- To review and analyze genetic screens (in vitro and in vivo) for tumor immune sensitivity.
- To highlight commonly identified proteins and pathways involved in tumor-intrinsic immune susceptibility.
Main Methods:
- Overview of functional genetic screens using CRISPR-Cas9.
- Comparative analysis of commonly identified proteins and pathways across studies.
- In vitro and in vivo experimental approaches.
Main Results:
- CRISPR screens identified key regulators of tumor cell immune sensitivity.
- Commonly identified pathways include antigen presentation, interferon-gamma, tumor necrosis factor, and autophagy.
- Demonstrated importance of these pathways in tumor cell sensitivity to immune attack.
Conclusions:
- Genetic screens underscore the critical role of specific pathways in tumor immune susceptibility.
- These studies reveal complex tumor cell-microenvironment interactions.
- Insights provide fundamental and clinical understanding of tumor immune resistance mechanisms.
