Zodiac (case 2): Immune Check Point Genes in Cancer

This is the 2nd-article of a blog series aiming to introduce Zodiac, a comprehensive tool that reveals genetic interactions in cancer by big-data computation. An introduction of Zodiac is in the 1st article here.

A novel therapeutic strategy that tackles a critical immune-modulating mechanism has recently risen to the forefront of cancer immunotherapy: the blockade of the inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA4),  programmed death-1 (PD1, or PDCD1) and its ligand, PDL1 (CD274), an approach termed immune-checkpoint blockade. This treatment is designed to improve activation and effector function of tumor-specific T cells.

Zodiac shows that the expression of CTLA4 is strongly correlated with the expressions of genes related to immune cells and system, such as TCL1A, CD38, IKZF1, LYN, LAMP3, and CD5. See here.

For PD1, Zodiac shows strong co-expression of important genes such as PTPN7, CD6, and many other interesting cancer-related genes.  See here.

For PDL1, the list of co-expressed gene is equally intriguing, see here. Genes such as TP63, PI3KCG are positively correlated while TGFB1L1 (HIC5) and MME are negatively correlated.

Lastly, the three genes exhibit cross modality interactions (see here) in Zodiac, suggesting potential interplay among them in the cellular systems.

I hope these results will accelerate the discovery of new cancer immunotherapies by providing potential new drug targets.

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