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Project

Alternative RNA splicing as a predictor of response to checkpoint immunotherapy

Although several biomarkers predictive of immune checkpoint
blockade (ICB) have been proposed, they have insufficient predictive power
to be routinely applied in a diagnostic setting. Tumor mutation
burden (TMB), which correlates with tumor neoepitope load and antigenicity,
is one such biomarker. However, since TMB-low tumors can also respond to
ICB, other mechanisms (in addition to TMB) are likely to contribute to tumor
antigenicity. Here, we hypothesize that alternative splicing events in cancer
cells, similar to somatic mutations, contribute to the generation of
neoepitopes, thereby influencing outcome of cancer immunotherapy. We will
therefore explore at single-cell level the contribution of alternative splicing
events to neoepitope load. Also, we will assess the combined read-out of
alternative splicing and TMB on response prediction to ICB. As such, our
proposed work could facilitate the upfront detection of cancer patients
responding to ICB.

Date:1 Mar 2021 →  Today
Keywords:Predictive factors, biomarkers, immunotherapy, transcriptomics
Disciplines:Cancer diagnosis, Cancer therapy