High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival
Background: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/22/5783 |
| _version_ | 1797510949294309376 |
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| author | Alexandros Lalos Ornella Neri Caner Ercan Alexander Wilhelm Sebastian Staubli Alberto Posabella Benjamin Weixler Luigi Terracciano Salvatore Piscuoglio Sylvia Stadlmann Giulio C. Spagnoli Raoul A. Droeser Gad Singer |
| author_facet | Alexandros Lalos Ornella Neri Caner Ercan Alexander Wilhelm Sebastian Staubli Alberto Posabella Benjamin Weixler Luigi Terracciano Salvatore Piscuoglio Sylvia Stadlmann Giulio C. Spagnoli Raoul A. Droeser Gad Singer |
| author_sort | Alexandros Lalos |
| collection | DOAJ |
| description | Background: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment. Methods: We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months. Results: There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS (<i>p</i> = 0.008) and OS (<i>p</i> = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity (<i>p</i> = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24–0.99; <i>p</i> = 0.047) and OS (HR = 0.28; 95% CI 0.10–0.77; <i>p</i> = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles. Conclusions: The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration. |
| first_indexed | 2024-03-10T05:38:28Z |
| format | Article |
| id | doaj.art-8c772b4699c84f8d9b365a85477f6f46 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T05:38:28Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8c772b4699c84f8d9b365a85477f6f462023-11-22T22:43:16ZengMDPI AGCancers2072-66942021-11-011322578310.3390/cancers13225783High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall SurvivalAlexandros Lalos0Ornella Neri1Caner Ercan2Alexander Wilhelm3Sebastian Staubli4Alberto Posabella5Benjamin Weixler6Luigi Terracciano7Salvatore Piscuoglio8Sylvia Stadlmann9Giulio C. Spagnoli10Raoul A. Droeser11Gad Singer12University Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandUniversity Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandInstitute of Pathology, University Hospital Basel, 4056 Basel, SwitzerlandUniversity Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandUniversity Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandUniversity Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandDepartment of Surgery, Charité University Hospital, Campus Benjamin Franklin, 12203 Berlin, GermanyInstitute of Pathology, University Hospital Basel, 4056 Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, 4031 Basel, SwitzerlandInstitute of Pathology, Kantonsspital Baden AG, 5404 Baden, SwitzerlandIstituto CNR “Translational Pharmacology”, 00133 Rome, ItalyUniversity Center for Gastrointestinal and Liver Diseases, Clarunis, University of Basel, 4031 Basel, SwitzerlandInstitute of Pathology, Kantonsspital Baden AG, 5404 Baden, SwitzerlandBackground: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment. Methods: We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months. Results: There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS (<i>p</i> = 0.008) and OS (<i>p</i> = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity (<i>p</i> = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24–0.99; <i>p</i> = 0.047) and OS (HR = 0.28; 95% CI 0.10–0.77; <i>p</i> = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles. Conclusions: The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration.https://www.mdpi.com/2072-6694/13/22/5783ovarian cancerCD16tissue microarrayimmunohistochemistryprognosisbiomarker |
| spellingShingle | Alexandros Lalos Ornella Neri Caner Ercan Alexander Wilhelm Sebastian Staubli Alberto Posabella Benjamin Weixler Luigi Terracciano Salvatore Piscuoglio Sylvia Stadlmann Giulio C. Spagnoli Raoul A. Droeser Gad Singer High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival Cancers ovarian cancer CD16 tissue microarray immunohistochemistry prognosis biomarker |
| title | High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival |
| title_full | High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival |
| title_fullStr | High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival |
| title_full_unstemmed | High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival |
| title_short | High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival |
| title_sort | high density of cd16 tumor infiltrating immune cells in recurrent ovarian cancer is associated with enhanced responsiveness to chemotherapy and prolonged overall survival |
| topic | ovarian cancer CD16 tissue microarray immunohistochemistry prognosis biomarker |
| url | https://www.mdpi.com/2072-6694/13/22/5783 |
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