• Oncol Lett · Dec 2019

    A subset of patients with MSS/MSI-low-colorectal cancer showed increased CD8(+) TILs together with up-regulated IFN-γ.

    • Tomohiro Kikuchi, Kosaku Mimura, Hirokazu Okayama, Yuko Nakayama, Katsuharu Saito, Leo Yamada, Eisei Endo, Wataru Sakamoto, Shotaro Fujita, Hisahito Endo, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze, Shinji Ohki, and Koji Kono.
    • Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
    • Oncol Lett. 2019 Dec 1; 18 (6): 5977-5985.

    AbstractA small subset of patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS)-colorectal cancer (CRC) benefit from immunotherapy with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade. Therefore, the aim of the current study was to evaluate the immune status of patients with pMMR/microsatellite instability-low (MSI-L)/MSS-CRC and deficient MMR (dMMR)/MSI-high (MSI-H)-CRC in order to identify responders to anti-PD-1/PD-L1 inhibitors. The current study used a dataset downloaded from The Cancer Genome Atlas (TCGA) as well as 219 clinical tissue samples to investigate the infiltrating grade of cluster of differentiation (CD) 4 and CD8 tumor infiltrating lymphocytes (TILs), the expression levels of PD-L1 and PD-L2, the interferon-γ (IFN-γ) and CD8 T effector gene signatures, and the phosphorylated signal transducer and activator of transcription 1 (p-STAT1) status in patients with pMMR/MSI-L/MSS-CRC and dMMR/MSI-H-CRC. Analysis of TCGA dataset revealed that the mRNA expression levels of PD-L1 and PD-L2, the IFN-γ gene signature and the CD8 T effector gene signature were significantly upregulated in MSI-H tumors compared with MSI-L/MSS tumors. Additionally, a subpopulation of patients with upregulation of the IFN-γ and CD8 T effector gene signatures was observed in those with MSI-L/MSS-CRC. Immunohistochemical staining of the clinical samples revealed a subpopulation of patients with pMMR-CRC that were positive for PD-L1 and p-STAT1, and whom had levels of elevated CD8(+) and CD4(+) TILs infiltration similar to those observed in patients with dMMR-CRC. The results obtained in the current study suggested that a subpopulation of patients with MSI-L/MSS-CRC and pMMR-CRC with upregulated IFN-γ and CD8 T effector gene signatures may benefit from immunotherapy with antibodies against PD-1 and PD-L1.Copyright: © Kikuchi et al.

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