This is why I’m hot.

Despite tremendous advances in immunotherapy, we still have a pretty rudimentary understanding of how the whole cancer/immune system interaction works. The TRACERx initiative is a big, prospective translational research study exploring cancer evolution. Here we have some interesting findings from Lung TRACERx investigating how untreated lung tumors develop immune evasiveness. They describe what appears to be an immunologically “hot” micro-environment early in lung tumor development where there is extensive immune infiltration driven by “normal” presentation of tumor neoantigens. What happens next is intense evolutionary pressure for tumor subclones with repressed neoantigen presentation, airising in two forms: reduced production of neoantigens and loss of antigen presentation machinery. These subclones then selectively expand by evading immune surveillance and reducing immune infiltrate and genomic diversification. TBL: The immune system exerts strong selective pressure on early lung tumors to develop multiple evasive mechanisms such as decreased neoantigen production or presentation. | Rosenthal, Nature 2019


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