Nature Medicine | Spoonful of Medicine

Mutants, revertants and innate responders

Two sets of papers caught my attention over the past couple of days. Apologies if they are old hat for those of you who work in these fields. It’s hard to keep up with all the ToC alerts I get.

The first is a doublet from Nature on the mechanism whereby certain tumors acquire resistence to chemotherapy. The studies, by Wataru Sakai and colleagues and by Stacey Edwards and colleagues focused on tumors that carry mutations in BRCA2 and are therefore sensitive to platinum compounds like cisplatin. In some cases, these tumors develop resistance to cisplatin, and what both studies show is that the development of resistance depends on the appearance of new mutations in BRCA2, which restore the open reading frame of the protein. Although this is perhaps not incredibly surprising, particularly because similar secondary mutations had been observed in cases of resistance to imatinib in leukemia, this finding has obvious clinical implications for people who become unresponsive to cisplatin.

The other paper, by Marielle Gold and her colleagues in PLoS Pathogens, reports on the existence of a novel population of human T cells that innately recognize Mycobacterium tuberculosis (Mtb). These cells, which the authors isolated from newborns who were very unlikely to have ever been exposed to the bacterium, exist at relatively high frequencies and respond to Mtb-infected cells by producing IFN-γ. The authors assert that this is the first demonstration of a human innate pathogen-specific T cell and refer to preliminary experiments showing that other thymocytes can also respond to other pathogens including Staphylococcus aureus and Escherichia coli. How this innate recognition comes about in the fisst place strikes me as a pretty interesting question for follow-up studies.

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