Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion
Cartilage oligomeric matrix protein (COMP) is an emerging regulator of tumor progression. The aim of this study was to evaluate the expression of COMP in periampullary adenocarcinoma with respect to prognostic value for survival and relapse, levels of fibrosis and infiltrating immune cells. COMP exp...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2111906 |
| _version_ | 1817998479080816640 |
|---|---|
| author | Konstantinos S. Papadakos Sebastian Lundgren Chrysostomi Gialeli Patrick Micke Artur Mezheyeuski Jacob Elebro Karin Jirström Anna M. Blom |
| author_facet | Konstantinos S. Papadakos Sebastian Lundgren Chrysostomi Gialeli Patrick Micke Artur Mezheyeuski Jacob Elebro Karin Jirström Anna M. Blom |
| author_sort | Konstantinos S. Papadakos |
| collection | DOAJ |
| description | Cartilage oligomeric matrix protein (COMP) is an emerging regulator of tumor progression. The aim of this study was to evaluate the expression of COMP in periampullary adenocarcinoma with respect to prognostic value for survival and relapse, levels of fibrosis and infiltrating immune cells. COMP expression was evaluated using immunohistochemistry in primary tumors and subsets of paired lymph node metastases in tissue microarrays including 175 patients with periampullary adenocarcinoma. Collagen content was assessed with Sirius Red-Fast Green staining. High COMP levels were detected in cancer cells and in stroma, in 46% and 57% of the patients, respectively. High COMP expression was strongly associated with more aggressive pancreatobiliary-type (PB-type) compared to intestinal-type tumors (p < .0001). Importantly, high expression of COMP correlated with the exclusion of cytotoxic T-cells from the cancer cell compartment of the tumors, particularly in PB-type tumors. Higher levels of fibrosis measured by the density of collagen fibers correlated with high COMP levels in both cancer cells and stroma. This in turn could lead to exclusion of cytotoxic T-cells from accessing the cancer cells, a recognized immunotherapy resistance mechanism. Targeting COMP could therefore be considered as a novel therapeutic strategy in PB-type periampullary adenocarcinoma. |
| first_indexed | 2024-04-14T02:53:34Z |
| format | Article |
| id | doaj.art-5534b29284d848cdb083d0459b839d54 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-14T02:53:34Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-5534b29284d848cdb083d0459b839d542022-12-22T02:16:11ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2111906Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusionKonstantinos S. Papadakos0Sebastian Lundgren1Chrysostomi Gialeli2Patrick Micke3Artur Mezheyeuski4Jacob Elebro5Karin Jirström6Anna M. Blom7Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, SwedenDepartment of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, SwedenDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, SwedenDepartment of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, SwedenDepartment of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, SwedenDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, SwedenCartilage oligomeric matrix protein (COMP) is an emerging regulator of tumor progression. The aim of this study was to evaluate the expression of COMP in periampullary adenocarcinoma with respect to prognostic value for survival and relapse, levels of fibrosis and infiltrating immune cells. COMP expression was evaluated using immunohistochemistry in primary tumors and subsets of paired lymph node metastases in tissue microarrays including 175 patients with periampullary adenocarcinoma. Collagen content was assessed with Sirius Red-Fast Green staining. High COMP levels were detected in cancer cells and in stroma, in 46% and 57% of the patients, respectively. High COMP expression was strongly associated with more aggressive pancreatobiliary-type (PB-type) compared to intestinal-type tumors (p < .0001). Importantly, high expression of COMP correlated with the exclusion of cytotoxic T-cells from the cancer cell compartment of the tumors, particularly in PB-type tumors. Higher levels of fibrosis measured by the density of collagen fibers correlated with high COMP levels in both cancer cells and stroma. This in turn could lead to exclusion of cytotoxic T-cells from accessing the cancer cells, a recognized immunotherapy resistance mechanism. Targeting COMP could therefore be considered as a novel therapeutic strategy in PB-type periampullary adenocarcinoma.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2111906COMPpancreatic cancerimmune cell exclusionfibrosiscollagen |
| spellingShingle | Konstantinos S. Papadakos Sebastian Lundgren Chrysostomi Gialeli Patrick Micke Artur Mezheyeuski Jacob Elebro Karin Jirström Anna M. Blom Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion OncoImmunology COMP pancreatic cancer immune cell exclusion fibrosis collagen |
| title | Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion |
| title_full | Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion |
| title_fullStr | Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion |
| title_full_unstemmed | Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion |
| title_short | Expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary-type morphology, higher levels of fibrosis and immune cell exclusion |
| title_sort | expression of cartilage oligomeric matrix protein in periampullary adenocarcinoma is associated with pancreatobiliary type morphology higher levels of fibrosis and immune cell exclusion |
| topic | COMP pancreatic cancer immune cell exclusion fibrosis collagen |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2111906 |
| work_keys_str_mv | AT konstantinosspapadakos expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT sebastianlundgren expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT chrysostomigialeli expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT patrickmicke expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT arturmezheyeuski expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT jacobelebro expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT karinjirstrom expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion AT annamblom expressionofcartilageoligomericmatrixproteininperiampullaryadenocarcinomaisassociatedwithpancreatobiliarytypemorphologyhigherlevelsoffibrosisandimmunecellexclusion |