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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ovarian cancer CD16 tissue microarray immunohistochemistry prognosis biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8c772b4699c84f8d9b365a85477f6f46
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8c772b4699c84f8d9b365a85477f6f46
record_format	dspace
spelling	oai:doaj.org-article:8c772b4699c84f8d9b365a85477f6f462021-11-25T17:03:57ZHigh Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival10.3390/cancers132257832072-6694https://doaj.org/article/8c772b4699c84f8d9b365a85477f6f462021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5783https://doaj.org/toc/2072-6694Background: 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.Alexandros LalosOrnella NeriCaner ErcanAlexander WilhelmSebastian StaubliAlberto PosabellaBenjamin WeixlerLuigi TerraccianoSalvatore PiscuoglioSylvia StadlmannGiulio C. SpagnoliRaoul A. DroeserGad SingerMDPI AGarticleovarian cancerCD16tissue microarrayimmunohistochemistryprognosisbiomarkerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5783, p 5783 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian cancer CD16 tissue microarray immunohistochemistry prognosis biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ovarian cancer CD16 tissue microarray immunohistochemistry prognosis biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
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_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_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_sort	high density of cd16+ tumor-infiltrating immune cells in recurrent ovarian cancer is associated with enhanced responsiveness to chemotherapy and prolonged overall survival
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8c772b4699c84f8d9b365a85477f6f46
work_keys_str_mv	AT alexandroslalos highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT ornellaneri highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT canerercan highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT alexanderwilhelm highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT sebastianstaubli highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT albertoposabella highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT benjaminweixler highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT luigiterracciano highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT salvatorepiscuoglio highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT sylviastadlmann highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT giuliocspagnoli highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT raouladroeser highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival AT gadsinger highdensityofcd16tumorinfiltratingimmunecellsinrecurrentovariancancerisassociatedwithenhancedresponsivenesstochemotherapyandprolongedoverallsurvival
_version_	1718412788513112064

High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival

Ejemplares similares