Efficacy of immune checkpoint blockade in MUTYH-associated hereditary colorectal cancer.

Investigational New Drugs
Nikita M VolkovEvgeny N Imyanitov

Abstract

Colorectal carcinomas (CRCs) caused by hereditary biallelic MUTYH gene mutations are characterized by elevated mutation load and high lymphocyte infiltration. Given that these tumor features are associated with the response to immune checkpoint inhibitors, we administered nivolumab to a CRC patient who carried two inactive MUTYH alleles (p.Y179C and p.G396D) and previously experienced failure of chemotherapy. This experimental treatment resulted in a pronounced tumor response. We further compared tumor lymphocyte infiltration in MUTYH-associated (n = 3), high-level microsatellite instability (MSI-H, n = 8) and microsatellite stable (MSS, n = 6) CRCs. Both MUTYH-driven and MSI-H CRCs showed noticeably higher lymphocyte densities than those of microsatellite stable tumors; this difference reached the level of statistical significance for the comparison of central areas of the tumors (p = 0.02 and 0.03, respectively) but not for the invasive tumor margins. Although MUTYH-associated tumors are exceptionally rare among unselected CRC cases, their share in CRC patients with somatic KRAS p.G12C substitution approaches 5-25%. These observations provide a rationale for further evaluation of the efficacy of the immune checkpoint blockade...Continue Reading

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Citations

May 10, 2020·International Journal of Cancer. Journal International Du Cancer·Daniele CaraccioloPierfrancesco Tassone
Jan 10, 2021·Diagnostics·Megan L HutchcraftJill M Kolesar
Apr 4, 2021·Cells·Maria Daca AlvarezLaura Valle

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