Endogenous Retrovirus Expression, Chromatin Abnormalities, and Response to Immune Checkpoint Blockade in Clear Cell Renal Cell Cancer
[Technical Report, Annual Report]
RUTGERS - THE STATE UNIV NEW BRUNSWICK NJ
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In this study, we investigate the role of re-expression of endogenous retroviruses ERV as an alternative mechanism of immune activation that may be relevant in ccRCC. Our preliminary data demonstrate that ERVs, including ERV3.2 are highly expressed in a subset of ccRCC and this expression is associated with evidence of CD8 T-cell infiltration and with response to single agent immune checkpoint blockade. We have found that a subset of ccRCC have increased expression of specific immune checkpoints including LAG3, suggesting that novel LAG3 antibodies may be active in ccRCC. Treatment of ccRCC cell lines and models with epigenetic modifying agents can increase ERV expression. Analyses is ongoing in both cell models and tissue specimens to further investigate how ERV expression is associated with both chromatin changes and immune activation in renal cancer. Our overall aim is to investigate the mechanisms of dysregulated ERV expression in a subset of ccRCC and could function and its potential role as a biomarker of response to ICB.
- Medicine and Medical Research
- Anatomy and Physiology