PMID- 33240416
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201127
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Jan
TI  - Siglec-7 is a predictive biomarker for the efficacy of cancer vaccination against 
      metastatic colorectal cancer.
PG  - 10
LID - 10.3892/ol.2020.12271 [doi]
LID - 10
AB  - Cancer immunotherapy, including vaccination, is considered a major scientific and 
      medical breakthrough. However, cancer immunotherapy does not result in durable 
      objective responses against colorectal cancer (CRC). To improve the efficacy of 
      immunotherapy, the present study investigated several biomarkers for selecting 
      patients who were expected to respond well to immunotherapy. Firstly, a 
      comprehensive proteomic analysis was performed using tumor tissue lysates from 
      patients enrolled in a phase II study, in which five human leukocyte antigen 
      (HLA)-A*24:02-restricted peptides were administered. Sialic acid-binding 
      immunoglobulin type lectin (Siglec)-7 was identified as a potential predictive 
      biomarker. Subsequently, this biomarker was validated using western blot 
      analysis, and immunofluorescence using tissue samples from the patients enrolled 
      in the phase II study. The expression levels of Siglec-7 detected by 
      immunofluorescence were quantified and their association with overall survival 
      (OS) in patients treated with the peptide vaccine was examined. Furthermore, 
      considering the important role of tumor-infiltrating lymphocytes (TILs) for CRC 
      prognosis, the densities of CD3(+), CD4(+,) CD8(+) and forkhead box P3 (FOXP3)(+) 
      T cells in CRC tissues were examined and compared with Siglec-7 expression. The 
      mean expression levels of Siglec-7 were significantly higher in patients with 
      poor prognosis, with an OS of </=2 years, as shown in comprehensive proteomic 
      analysis (P=0.016) and western blot analysis (P=0.025). Immunofluorescence 
      analysis demonstrated that Siglec-7 was expressed in intratumoral macrophages. 
      The OS in patients with high Siglec-7 expression was significantly shorter than 
      in that in patients with low Siglec-7 expression (P=0.017) in the 
      HLA-A*24:02-matched patients. However, this difference was not observed in the 
      HLA-unmatched patients. There was no significant difference in OS between 
      patients according to the numbers of TILs, nor significant correlation between 
      TILs and Siglec-7 expression. In conclusion, Siglec-7 expression in macrophages 
      in tumor tissue may be a novel predictive biomarker for the efficacy of 
      immunotherapy against metastatic CRC.
CI  - Copyright: (c) Yamada et al.
FAU - Yamada, Kensuke
AU  - Yamada K
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Hazama, Shoichi
AU  - Hazama S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
AD  - Department of Translational Research and Developmental Therapeutics Against 
      Cancer, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Suzuki, Nobuaki
AU  - Suzuki N
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Xu, Ming
AU  - Xu M
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Nakagami, Yuki
AU  - Nakagami Y
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
AD  - Department of Translational Research and Developmental Therapeutics Against 
      Cancer, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Fujiwara, Nobuyuki
AU  - Fujiwara N
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Tsunedomi, Ryouichi
AU  - Tsunedomi R
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Yoshida, Shin
AU  - Yoshida S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Tomochika, Shinobu
AU  - Tomochika S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Matsukuma, Satoshi
AU  - Matsukuma S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Matsui, Hiroto
AU  - Matsui H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Tokumitsu, Yukio
AU  - Tokumitsu Y
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Kanekiyo, Shinsuke
AU  - Kanekiyo S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Shindo, Yoshitaro
AU  - Shindo Y
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Watanabe, Yusaku
AU  - Watanabe Y
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Iida, Michihisa
AU  - Iida M
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Takeda, Shigeru
AU  - Takeda S
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Ioka, Tatsuya
AU  - Ioka T
AD  - Oncology Center, Yamaguchi University Hospital, Ube, Yamaguchi 755-8505, Japan.
FAU - Ueno, Tomio
AU  - Ueno T
AD  - Department of Gastroenterological Surgery, Kawasaki Medical School, Kurashiki, 
      Okayama 701-0192, Japan.
FAU - Ogihara, Hiroyuki
AU  - Ogihara H
AD  - Division of Electrical, Electronic and Information Engineering, Graduate School 
      of Sciences and Technology for Innovation, Yamaguchi University, Ube, Yamaguchi 
      755-8611, Japan.
FAU - Hamamoto, Yoshihiko
AU  - Hamamoto Y
AD  - Division of Electrical, Electronic and Information Engineering, Graduate School 
      of Sciences and Technology for Innovation, Yamaguchi University, Ube, Yamaguchi 
      755-8611, Japan.
FAU - Hoshii, Yoshinobu
AU  - Hoshii Y
AD  - Department of Diagnostic Pathology, Yamaguchi University Hospital, Ube, Yamaguchi 
      755-8505, Japan.
FAU - Kawano, Hiroo
AU  - Kawano H
AD  - Department of Basic Laboratory Sciences, Yamaguchi University Graduate School of 
      Medicine, Ube, Yamaguchi 755-8505, Japan.
FAU - Fujita, Tomonobu
AU  - Fujita T
AD  - Division of Cellular Signaling, Institute for Advanced Medical Research, Keio 
      University School of Medicine, Tokyo 160-8582, Japan.
FAU - Kawakami, Yutaka
AU  - Kawakami Y
AD  - Division of Cellular Signaling, Institute for Advanced Medical Research, Keio 
      University School of Medicine, Tokyo 160-8582, Japan.
FAU - Nagano, Hiroaki
AU  - Nagano H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201103
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC7681234
OTO - NOTNLM
OT  - biomarker
OT  - colorectal cancer
OT  - peptide vaccine
OT  - protein expression analysis
OT  - sialic acid-binding immunoglobulin type lectin-7
EDAT- 2020/11/27 06:00
MHDA- 2020/11/27 06:01
PMCR- 2020/11/03
CRDT- 2020/11/26 05:46
PHST- 2020/05/28 00:00 [received]
PHST- 2020/09/29 00:00 [accepted]
PHST- 2020/11/26 05:46 [entrez]
PHST- 2020/11/27 06:00 [pubmed]
PHST- 2020/11/27 06:01 [medline]
PHST- 2020/11/03 00:00 [pmc-release]
AID - OL-0-0-12271 [pii]
AID - 10.3892/ol.2020.12271 [doi]
PST - ppublish
SO  - Oncol Lett. 2021 Jan;21(1):10. doi: 10.3892/ol.2020.12271. Epub 2020 Nov 3.