Genes Behind Tumor Immunity Revealed by CRISPR Imaging

Genes Behind Tumor Immunity Revealed by CRISPR Imaging ...

Scientists in Mount Sinai have developed a new technology to enable them to connect specific genes to complex tumor characteristics at an improbable scale and resolution. These findings might lead to new approaches for tackling anti-cancer medications.

According to a March issue ofCell, a genetic barcode system will mark cancer cells with different gene modifications and image the cancer cells, as well as other adjacent non-cancer cells. Using this technique, researchers were able to identify specific genes that regulate lung tumor growth, immune composition, and even response to immunotherapy.

Cancer treatment has been revolutionized by immunotherapies such as Keytruda and Tecentriq, which turn on immune cells in the tumor and enable them to kill cancer cells, and Avastin, which alters the tumors blood vessels and feeds the cancer.

Because the tumors environment has such a large effect on patient outcomes, there is a pressing need to identify cancer genes that are used in their local ecosystem. This information is crucial to developing new anti-cancer medications. However, finding the genes to target is required by a large scale of research that has been very difficult to achieve in animal models of cancer, which is essential for faithfully representing the entire cell ecosystem of a patient tumor.

Genetic scans have enabled people to identify genes and functions within the cancer cells for years, but these are not the ones who have access to gene editing technology. This has left many critical questions unanswered by genetic screens.

The researchers identified two key pathways that had significant implications on tumor growth as well as tumor architecture and immune cell recruitment. When theTGFbR2gene or a gene coding forSOCS1, a regulator of IFNg were removed from the cancer cells, the lung tumors became larger and more abundant.

Although the loss of either gene has similar effects on tumor growth, imaging of the tumors, which was made possible by the Perturb map platform, showed that theSOCS1tumors were highly infiltrated by T cells, while the TGFbR tumors were excluded. This is an important conclusion, as patients whose tumors contain less immune cells respond worse to immunotherapy drugs.

According to senior author Brian Brown, PhD, the Director of the Icahn Genomics Institute, and the Director of the PrIISM at Mount Sinai, this is a significant insight because we are discovering that many patient tumors are composed of genetically distinct subclones. This may help as a pocket of resistance to immunotherapies like Keytruda, but the Perturb map platform will now provide scientists with the potential to address this problem.

The Perturb-map is allowing us to identify the specific genes that control a tumors environment at an unprecedented rate. This includes allowing us to identify the genes that are responsible for recruiting or reprogramming cells that prevent the immune system from eliminating tumors. Miriam Merad, MD, PhD, has been shown to be a good addition to the study''s director and the Foundation for Excellence in Cancer. This is going to greatly increase our ability to identify new targets for improved cancer therapies and that is vital for our

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