Cancer Discovery: Zou Weiping's team reveals the mechanism by which the loss of optic neuroprotein mediates immune escape in colorectal cancer

Although immunotherapy has made important progress in melanoma and lung cancer, it has little benefit in colorectal cancer.

Studies have shown that abnormalities in the interferon gamma (IFN gamma) and antigen presentation (MHC-I) pathways are one of the main causes of tumor immune escape and immunotherapy resistance.

On February 24, 2021, the team of Professor Weiping Zou from the University of Michigan (Dr.

The study revealed that optic nerve protein (optineurin) is a key node that regulates the integrity of colorectal cancer IFNγ and MHC-I pathways.

In this study, the researchers found that the expression of optineurin was positively correlated with IFNγ and MHC-I pathways through bioinformatics analysis.

Further exploration found that the expression of optineurin had been reduced as early as in the adenoma tissues of colorectal precancerous lesions, and the abundance of optineurin expression was negatively correlated with the pathological grade and clinical stage of colorectal cancer.

To explore the function of optineurin in colorectal cancer, the researchers constructed a variety of mouse tumor models with defects in optineurin expression.

As we all know, tumor antigen peptides form a complex with MHC-I, expressed on the cell surface and presented to CD8+ T cells, and combined with TCR on the surface of T cells to activate T cells.

So how does AP3D1 recognize and transport IFNGR1 to lysosomal degradation? Previous studies have shown that AP3D1 can recognize palmitoylated proteins and promote their lysosomal transport [5].

Optineurin competes with AP3D1 to protect palmitoylated IFNGR1 from lysosomal sorting and degradation

In summary, this study reveals the effect of optineurin on colorectal cancer immunity and immunotherapy response.

Original source:

Wan Du, Fang Hua, Xiong Li, et al.