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Effect of preoperative chemoradiotherapy on the immunological status of rectal cancer patients

2020; Oxford University Press; Volume: 61; Issue: 5 Linguagem: Inglês

10.1093/jrr/rraa041

1349-9157

K. Yasui, Ryota Kondou, Akira Iizuka, Haruo Miyata, Emiko Tanaka, Tadashi Ashizawa, Takeshi Nagashima, Keiichi Ohshima, Kenichi Urakami, Masatoshi Kusuhara, Koji Muramatsu, Takashi Sugino, Ken Yamguchi, Keita Mori, Hideyuki Harada, Tetsuo Nishimura, Hiroyasu Kagawa, Yushi Yamakawa, Hitoshi Hino, Akio Shiomi, Yasuto Akiyama,

Colorectal and Anal Carcinomas

Abstract 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.