(Mis)matching tumors to immunotherapy

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Science  10 Jul 2015:
Vol. 349, Issue 6244, pp. 151-152
DOI: 10.1126/science.349.6244.151-c

Despite the amazing success stories seen in some patients receiving cancer immunotherapy, the sobering reality is that not all patients or cancer types respond. For instance, colorectal cancer does not respond in the dramatic way that melanomas and other cancers do to the so-called “immune checkpoint inhibitors.” A subset of colorectal cancers cannot repair mismatched bases in DNA and therefore harbor high levels of somatic mutations. In a small clinical trial, Le et al. found that patients with mismatch repair–deficient colorectal tumors responded more favorably to an immune checkpoint inhibitor than those with mismatch repair–proficient tumors. The greater response observed in the former group is probably due to a higher abundance of mutation-associated neoantigens that boost antitumor immunity.

N. Engl. J. Med. 372, 2509 (2015).

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