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Immune landscape analysis to identify targets for immunotherapy across human carcinomas

      Background: Tumor-infiltrating lymphocytes (TILs) are restrained by the tumor environment thereby precluding tumor rejection. If similar deviations in the rejection capacity of TILs can be identified across different tumor entities, this would open the way for anti-tumor immunotherapy. Functional non-responsiveness can be mediated through multiple non-exclusive mechanisms including exhaustion, tolerance, anergy or cellular inhibition. We have previously described that CD8+ TILs of clear cell renal cell carcinoma (ccRCC) show an anergic phenotype with high levels of diacylglycerol kinase-α (DGK-α) and low levels of extracellular-signal regulated kinase (ERK) phosphorylation associated with lack of cytotoxic function and inability to respond to CD3 stimulation [1].The goal of this project is to analyze the immune infiltrate in ccRCC and non-virus associated hepatocellular carcinoma (nv-HCC) patients.
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