Immune Profiling Of Ectopic Lymphoid-Like Structures In Hepatocellular Carcinoma

Introduction:

Ectopic lymphoid-like structures (ELSs) are exquisitely arranged complexes of immune cells that form de novo in tissues and serve as frontal command posts for mounting local immune responses. While they provide immunological protection they are often associated with pathological inflammation. While abundant ELSs were previously shown to be correlated with good prognosis in colorectal cancerand melanoma, we recently discovered that ELSs have an opposite role in hepatocellular carcinoma (HCC). Hepatic ELSs can serve as micro-niches that support growth of liver cancer progenitor cells. This was accomplished using mice persistently expressing the NFκ-B pathway in hepatocytes, which feature abundant hepatic ELSs, closely phenocopying histopathological and molecular features of ELSs in chronically inflamed human livers.

Materials and Methods:

In order to test the contribution of specific immune cells of the ELS to cancer progenitor growth, we performed single cell RNA sequencing on isolated ELSs as well as validations of the populations identified, using flow cytometry analysis and immunostainings.

Results and Discussion:

We have identified a population of CD8 positive cells in ELSs, showing markers of T cell exhaustion. Importantly, treatment of ELSs with checkpoint blockade therapy prior to tumor formation, reduced HCC load.

Conclusion:

Our results might suggest that CD8 T cell exhaustion contributes to the pro-tumorigenic function of the ELSs in HCC formation. Reinvigoration of these CD8 cells by checkpoint blockade treatment may be a useful tool for preventing the pro-tumorigenic function of the ELS and a means for HCC prevention in particular clinical setups.