MCT11: A Novel Metabolic Target To Combat T Cell Exhaustion

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T cell exhaustion can severely hinder anti-cancer immune responses and several therapeutic modalities – including the most successful drug in medicine Merck’s KEYTRUDA – are designed to combat it.

A paper published in Nature Immunology on November 8th our of the University of Pittsburgh describes how exhausted T cells will upregulate their expression of monocarboxylate transporter 11 (MCT11), that they then use to “consume” high levels of lactic acid.

This acid influx enforces the onset of exhaustion, resulting in reduced T cell function. Blocking this interaction with an antibody improved intratumoral T cell function and augmented the therapeutic activity of PD-1 targeting antibodies. Also, an MCT11 antibody improved the therapeutic efficacy of CD19-targeting CAR-T cells.

These results highlight the potential of combining PD-1 antibodies or CAR-T cells with MCT11-targeting therapies to improve outcomes.

For more details, check out the full study and the lead author’s university homepage in the top comment below!