Immune profiling of microsatellite instability-high and polymerase ε (POLE)-mutated metastatic colorectal tumors identifies predictors of response to anti-PD-1 therapy.

Journal of Gastrointestinal Oncology
Chongkai WangMarwan Fakih

Abstract

Microsatellite instability-high (MSI-H) and polymerase ε (POLE)-mutated metastatic colorectal cancer (mCRC) represent hypermutated and ultramutated tumor phenotypes, respectively, that may predict benefit to checkpoint blockade [anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1)]. Immune profiling through multispectral fluorescent immunohistochemistry (IHC) using a multi-marker staining panel was performed on pretreatment tumor specimens from a cohort of MSI-H or POLE-mutated mCRC patients treated with PD-1 blockade at our institution to identify candidate predictors of response to checkpoint inhibitors. From 4/2013 to 1/2017, a total of 237 mCRC patients with molecularly profiled tumors were screened. Five MSI-H and three POLE-mutated mCRC patients were treated with checkpoint inhibitors. Immune profiling identified higher CD8+ tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME) of responders (CR or PR as best response) than nonresponders (SD or PD as best response). Responders had significantly higher densities of CD8+ PD-1+ TILs than nonresponders (P=0.0007). PD-L1 expression (P=0.73), CD4+ T-cell density (P=0.39), and CD4+ FOXP3+ T-cell density (P=0.68) did not significantly diff...Continue Reading

Citations

Feb 26, 2019·Journal of Surgical Oncology·Jaideep SandhuMarwan Fakih
Feb 5, 2019·Molecular Oncology·Nicole M ReillyAlberto Bardelli
Jun 26, 2020·Journal of Pathology and Translational Medicine·Jeong Mo BaeGyeong Hoon Kang
Apr 9, 2020·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Lisa A FriedmanAnne M Mills
Oct 31, 2020·Cancer Cell·Denis L JardimRazelle Kurzrock
Nov 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John H StricklerMustafa Khasraw
May 26, 2021·Expert Opinion on Biological Therapy·Chongkai Wang, Marwan Fakih
Jul 30, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jingjing FanZhi-Xiang Xu
Oct 6, 2021·Journal for Immunotherapy of Cancer·Hee Sang HwangJene Choi

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