Posts Tagged ‘selectively’


The present invention provides, inter alia, a method for identifying an agent that selectively decreases the number of cancer stem cells (CSCs). This method includes (a) contacting a CSC from a population of cells with a candidate agent; and (b) determ…

Neoantigen landscape dynamics during human melanoma–T cell interactions

Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T cell checkpoint blockade and adoptive T cell therapy8,14,15,19,20,26,27. Therefore, strategies to selectively enhance T cell reactivity against genetically defined neoantigens3,8,12,21,25 are currently under development. In mouse models, T cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens17,18. However, whether the T-cell-recognized neoantigen repertoire in human cancers is constant over time is unclear. Here we analyse the stability of neoantigen-specific T cell responses and the antigens they recognize in two stage IV melanoma patients treated by adoptive T cell transfer. The T-cell-recognized neoantigens can selectively be lost from the tumour cell population, either by overall reduced expression of the gene or loss of the mutant allele. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of a novel neoantigen-specific T cell reactivity within tumour-infiltrating lymphocytes. These data demonstrate the dynamic nature of cancer–T cell interactions, suggestive of T-cell-mediated neoantigen immunoediting, and argue for the therapeutic induction of broad neoantigen-specific T cell responses to avoid tumour resistance.

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