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The prognostic and potentially immunomodulatory role of cartilage oligomeric matrix protein in patients with gastric and esophageal adenocarcinoma

Papadakos, Konstantinos S LU orcid ; Gorji-Bahri, Gilar LU ; Gialeli, Chrysostomi LU ; Hedner, Charlotta LU ; Hagerling, Catharina LU ; Svensson, Maria C LU ; Jeremiasen, Martin LU ; Borg, David LU ; Fristedt, Richard LU and Jirström, Karin LU orcid , et al. (2024) In Cancer Immunology Immunotherapy 73(5).
Abstract

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a novel regulator of the tumor microenvironment. Studies in colon cancer and pancreatobiliary adenocarcinoma have revealed COMP expression to be associated with decreased infiltration of immune cells in the tumor microenvironment. Herein, the expression of COMP was investigated in gastric and esophageal adenocarcinoma with particular reference to its the relationship with the immune microenvironment.

METHODS: COMP expression was evaluated in tissue microarrays representing primary tumors from 159 patients with chemo- and radiotherapy naïve esophageal and gastric adenocarcinoma and 67 matched samples of lymph node metastases using immunohistochemistry. Additionally, collagen... (More)

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a novel regulator of the tumor microenvironment. Studies in colon cancer and pancreatobiliary adenocarcinoma have revealed COMP expression to be associated with decreased infiltration of immune cells in the tumor microenvironment. Herein, the expression of COMP was investigated in gastric and esophageal adenocarcinoma with particular reference to its the relationship with the immune microenvironment.

METHODS: COMP expression was evaluated in tissue microarrays representing primary tumors from 159 patients with chemo- and radiotherapy naïve esophageal and gastric adenocarcinoma and 67 matched samples of lymph node metastases using immunohistochemistry. Additionally, collagen fibers were stained with Sirius Red and evaluated with the FIJI macro TWOMBLI algorithm.

RESULTS: The expression of COMP in cancer cells in the entire cohort was associated with shorter overall survival (OS) (p = 0.013) and recurrence-free survival (RFS) (p = 0.029), while COMP expression in the stroma was correlated with shorter RFS (p = 0.042). Similar correlations were found for patients with gastric adenocarcinoma, whereas COMP expression was not prognostic in esophageal adenocarcinoma. Further, in the entire cohort, the expression of COMP in the stroma was correlated with exclusion of different populations of immune cells (CD8+, CD3+, FoxP3+, CD20+) from the tumor microenvironment. Finally, higher density and alignment of collagen fibers were correlated with the expression of COMP in the stroma.

CONCLUSIONS: Expression of COMP in gastric and esophageal adenocarcinoma was correlated with shorter OS and RFS. A reduced number of immune cells infiltrated the tumor microenvironment when COMP expression was detected. This phenomenon could be attributed to the denser collagen deposits, a hallmark of tumor fibrosis observed in COMP-expressing tumors.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Cartilage Oligomeric Matrix Protein, Prognosis, Adenocarcinoma, Stomach Neoplasms, Collagen, Tumor Microenvironment, Esophageal Neoplasms
in
Cancer Immunology Immunotherapy
volume
73
issue
5
article number
93
publisher
Springer
external identifiers
  • scopus:85189172322
  • pmid:38563861
ISSN
1432-0851
DOI
10.1007/s00262-024-03656-y
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
630e8467-c1c3-4c3c-9595-beb549f06218
date added to LUP
2024-04-03 21:23:26
date last changed
2024-04-16 12:26:43
@article{630e8467-c1c3-4c3c-9595-beb549f06218,
  abstract     = {{<p>BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a novel regulator of the tumor microenvironment. Studies in colon cancer and pancreatobiliary adenocarcinoma have revealed COMP expression to be associated with decreased infiltration of immune cells in the tumor microenvironment. Herein, the expression of COMP was investigated in gastric and esophageal adenocarcinoma with particular reference to its the relationship with the immune microenvironment.</p><p>METHODS: COMP expression was evaluated in tissue microarrays representing primary tumors from 159 patients with chemo- and radiotherapy naïve esophageal and gastric adenocarcinoma and 67 matched samples of lymph node metastases using immunohistochemistry. Additionally, collagen fibers were stained with Sirius Red and evaluated with the FIJI macro TWOMBLI algorithm.</p><p>RESULTS: The expression of COMP in cancer cells in the entire cohort was associated with shorter overall survival (OS) (p = 0.013) and recurrence-free survival (RFS) (p = 0.029), while COMP expression in the stroma was correlated with shorter RFS (p = 0.042). Similar correlations were found for patients with gastric adenocarcinoma, whereas COMP expression was not prognostic in esophageal adenocarcinoma. Further, in the entire cohort, the expression of COMP in the stroma was correlated with exclusion of different populations of immune cells (CD8+, CD3+, FoxP3+, CD20+) from the tumor microenvironment. Finally, higher density and alignment of collagen fibers were correlated with the expression of COMP in the stroma.</p><p>CONCLUSIONS: Expression of COMP in gastric and esophageal adenocarcinoma was correlated with shorter OS and RFS. A reduced number of immune cells infiltrated the tumor microenvironment when COMP expression was detected. This phenomenon could be attributed to the denser collagen deposits, a hallmark of tumor fibrosis observed in COMP-expressing tumors.</p>}},
  author       = {{Papadakos, Konstantinos S and Gorji-Bahri, Gilar and Gialeli, Chrysostomi and Hedner, Charlotta and Hagerling, Catharina and Svensson, Maria C and Jeremiasen, Martin and Borg, David and Fristedt, Richard and Jirström, Karin and Blom, Anna M}},
  issn         = {{1432-0851}},
  keywords     = {{Humans; Cartilage Oligomeric Matrix Protein; Prognosis; Adenocarcinoma; Stomach Neoplasms; Collagen; Tumor Microenvironment; Esophageal Neoplasms}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{5}},
  publisher    = {{Springer}},
  series       = {{Cancer Immunology Immunotherapy}},
  title        = {{The prognostic and potentially immunomodulatory role of cartilage oligomeric matrix protein in patients with gastric and esophageal adenocarcinoma}},
  url          = {{http://dx.doi.org/10.1007/s00262-024-03656-y}},
  doi          = {{10.1007/s00262-024-03656-y}},
  volume       = {{73}},
  year         = {{2024}},
}