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

Autor: Yushi Yamakawa, Koji Muramatsu, Tetsuo Nishimura, Ken Yamguchi, Keiichi Ohshima, Hiroyasu Kagawa, Masatoshi Kusuhara, Kazuaki Yasui, Haruo Miyata, Keita Mori, Takeshi Nagashima, Ryota Kondou, Hideyuki Harada, Kenichi Urakami, Akira Iizuka, Emiko Tanaka, Tadashi Ashizawa, Takashi Sugino, Hitoshi Hino, Akio Shiomi, Yasuto Akiyama
Rok vydání: 2020
Předmět:
Male
Epithelial-Mesenchymal Transition
Colorectal cancer
Health
Toxicology and Mutagenesis
Apoptosis
Proinflammatory cytokine
tumor-infiltrating lymphocytes (TIL)
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
Immune system
Preoperative Care
Tumor Microenvironment
Regular Paper
medicine
Humans
chemoradiotherapy (CRT)
Radiology
Nuclear Medicine and imaging
tumor microenvironment (TME)
consensus molecular subtype (CMS)
Aged
030304 developmental biology
0303 health sciences
Tumor microenvironment
Radiation
Rectal Neoplasms
business.industry
Gene Expression Profiling
Cancer
Chemoradiotherapy
Middle Aged
medicine.disease
Immune checkpoint
Gene Expression Regulation
Neoplastic
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
Cancer research
Cytokines
AcademicSubjects/SCI00960
Immunohistochemistry
Female
AcademicSubjects/MED00870
business
epithelial-to-mesenchymal transition (EMT)
Zdroj: Journal of Radiation Research
ISSN: 1349-9157
0449-3060
DOI: 10.1093/jrr/rraa041
Popis: 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: OpenAIRE
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