Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer
Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural kil...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-02-01
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| Series: | Cancer Control |
| Online Access: | https://doi.org/10.1177/1073274820903383 |
| _version_ | 1797772229276073984 |
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| author | Fabian Haak Isabelle Obrecht Nadia Tosti Benjamin Weixler MD Robert Mechera MD Silvio Däster MD Marco von Strauss MD Tarik Delko MD Giulio C. Spagnoli Luigi Terracciano MD Giuseppe Sconocchia Markus von Flüe MD Marko Kraljević MD Raoul A. Droeser MD |
| author_facet | Fabian Haak Isabelle Obrecht Nadia Tosti Benjamin Weixler MD Robert Mechera MD Silvio Däster MD Marco von Strauss MD Tarik Delko MD Giulio C. Spagnoli Luigi Terracciano MD Giuseppe Sconocchia Markus von Flüe MD Marko Kraljević MD Raoul A. Droeser MD |
| author_sort | Fabian Haak |
| collection | DOAJ |
| description | Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration. |
| first_indexed | 2024-03-12T21:48:06Z |
| format | Article |
| id | doaj.art-40b2bf6e4b284da9b8499558941a8b9c |
| institution | Directory Open Access Journal |
| issn | 1073-2748 |
| language | English |
| last_indexed | 2024-03-12T21:48:06Z |
| publishDate | 2020-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Control |
| spelling | doaj.art-40b2bf6e4b284da9b8499558941a8b9c2023-07-26T07:03:21ZengSAGE PublishingCancer Control1073-27482020-02-012710.1177/1073274820903383Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal CancerFabian Haak0Isabelle Obrecht1Nadia Tosti2Benjamin Weixler MD3Robert Mechera MD4Silvio Däster MD5Marco von Strauss MD6Tarik Delko MD7Giulio C. Spagnoli8Luigi Terracciano MD9Giuseppe Sconocchia10Markus von Flüe MD11Marko Kraljević MD12Raoul A. Droeser MD13 Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Institute of Pathology, University Hospital Basel, Basel, Switzerland Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Institute of Translational Pharmacology, National Research Council, Rome, Italy Institute of Pathology, University Hospital Basel, Basel, Switzerland Institute of Translational Pharmacology, National Research Council, Rome, Italy Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandObjectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.https://doi.org/10.1177/1073274820903383 |
| spellingShingle | Fabian Haak Isabelle Obrecht Nadia Tosti Benjamin Weixler MD Robert Mechera MD Silvio Däster MD Marco von Strauss MD Tarik Delko MD Giulio C. Spagnoli Luigi Terracciano MD Giuseppe Sconocchia Markus von Flüe MD Marko Kraljević MD Raoul A. Droeser MD Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer Cancer Control |
| title | Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer |
| title_full | Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer |
| title_fullStr | Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer |
| title_full_unstemmed | Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer |
| title_short | Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer |
| title_sort | tumor infiltration by ox40 cells enhances the prognostic significance of cd16 cell infiltration in colorectal cancer |
| url | https://doi.org/10.1177/1073274820903383 |
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