Gastroenterology Xagena

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Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features

Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer.

Researchers have aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas ( HCCs ) to determine whether these types of agents might be effective against liver tumors.

HCC samples from 956 patients were analyzed.

Researchers have correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples.
They have validated the correlation in a validation set of 728 tumor samples.
Using data from 190 tumors in the Cancer Genome Atlas, researchers have correlated immune cell gene expression profiles with numbers of chromosomal aberrations ( based on single-nucleotide polymorphism array ) and mutations ( exome sequence data ).

Approximately 25% of hepatocellular carcinomas were found to have markers of an inflammatory response, with high expression levels of the CD274 molecule ( PD-L1 ) and programmed cell death 1 ( PD-1 ), markers of cytolytic activity, and fewer chromosomal aberrations.

Researchers called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 ( TGFB ) that mediate immunosuppression.

Researchers did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other hepatocellular carcinomas.

Conclusion: in an analysis of HCC samples from 956 patients, almost 25% to express markers of an inflammatory response were found.
2 subclasses were identified, characterized by adaptive or exhausted immune responses.
These findings indicate that some hepatocellular carcinomas might be susceptible to therapeutic agents designed to block the regulatory pathways in T cells, such as PD-L1, PD-1, or TGFB inhibitors. ( Xagena )

Sia D et al, Gastroenterology 2017; Epub ahead of print