Wednesday 21 October 2020

Beyond SNVs and indels for neoantigen prediction in cold tumours

Cancer immunotherapy, in particular checkpoint inhibitor (CPI) therapy, has drastically changed the oncology field which has evoked a complete shift of standard care regimens and overall improvement of treatment efficacy of cancer patients. Despite these promising results, many malignancies still do not respond at all to checkpoint immunotherapy exposing patients to unnecessary side effects and society to high costs.

This low response rate can be explained by the fact that some tumours are barely different from healthy cells due to a low mutation frequency, i.e. low mutational burden (MTB) malignancies, and often these tumours are immune deserted or cold tumours1. These patients mostly have no or very limited T-cell activity since the low amount of mutations cause a limited number of patient-specific antigens (neoantigens) to be present on the tumour cells that can trigger a tumour-directed response. Thus, treatment with CPIs is often useless as there are no T-cells to be reactivated.

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