| Autor: |
Yasui, Kazuaki, Kondou, Ryota, Iizuka, Akira, Miyata, Haruo, Tanaka, Emiko, Ashizawa, Tadashi, Nagashima, Takeshi, Ohshima, Keiichi, Urakami, Kenichi, Kusuhara, Masatoshi, Muramatsu, Koji, Sugino, Takashi, Yamguchi, Ken, Mori, Keita, Harada, Hideyuki, Nishimura, Tetsuo, Kagawa, Hiroyasu, Yamakawa, Yushi, Hino, Hitoshi, Shiomi, Akio, Akiyama, Yasuto |
| Zdroj: |
Journal of Radiation Research; September 2020, Vol. 61 Issue: 5 p766-775, 10p |
| Abstrakt: |
The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n= 9) and not-treated (n= 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR). Other markers associated with the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TIL) and immune checkpoint molecules, were investigated using immunohistochemistry (IHC). The clinical responses of preoperative CRT for 9 rectal cancer patients were all rated as stable disease, while the pathological tumor regression score (TRG) revealed 6 cases of grade2 and 3 cases of grade1. According to the genetic signature of colon cancers, treated tumors belonged to consensus molecular subtype (CMS)4, while not-treated tumors had signatures of CMS2 or 3. CRT-treated tumors showed significant upregulation of EMT-associated genes, such as CDH2, TGF-beta and FGF, and cancer stem cell-associated genes. Additionally, qPCR and IHC demonstrated a suppressive immunological status derived from the upregulation of inflammatory cytokines (IL-6, IL-10 and TGF-beta) and immune checkpoint genes (B7-H3 and B7-H5) and from M2-type macrophage accumulation in the tumor. The induction of EMT and immune-suppressive status in the tumor after strong CRT treatment urges the development of a novel combined therapy that restores immune-suppression and inhibits EMT, ultimately leading to distant metastasis control. |
| Databáze: |
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