Immune infiltrating cells in duodenal cancers
Abstract Background Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic opti...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-020-02508-4 |
| _version_ | 1818284261202984960 |
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| author | G. Donisi G. Capretti N. Cortese A. Rigamonti F. Gavazzi G. Nappo A. Pulvirenti M. Sollai P. Spaggiari A. Zerbi F. Marchesi |
| author_facet | G. Donisi G. Capretti N. Cortese A. Rigamonti F. Gavazzi G. Nappo A. Pulvirenti M. Sollai P. Spaggiari A. Zerbi F. Marchesi |
| author_sort | G. Donisi |
| collection | DOAJ |
| description | Abstract Background Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables. Methods Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected. Results In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4–63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036). Conclusions Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations. |
| first_indexed | 2024-12-13T00:49:59Z |
| format | Article |
| id | doaj.art-2b834be65a254851bea31c77e9a6d2d4 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T00:49:59Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2b834be65a254851bea31c77e9a6d2d42022-12-22T00:04:57ZengBMCJournal of Translational Medicine1479-58762020-09-011811910.1186/s12967-020-02508-4Immune infiltrating cells in duodenal cancersG. Donisi0G. Capretti1N. Cortese2A. Rigamonti3F. Gavazzi4G. Nappo5A. Pulvirenti6M. Sollai7P. Spaggiari8A. Zerbi9F. Marchesi10Section of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSSection of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSDepartment of Immunology and Inflammation, Humanitas Clinical and Research Center-IRCCSDepartment of Immunology and Inflammation, Humanitas Clinical and Research Center-IRCCSSection of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSSection of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSSection of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSDepartment of Pathology, Humanitas Clinical and Research Center-IRCCSDepartment of Pathology, Humanitas Clinical and Research Center-IRCCSSection of Pancreatic Surgery, Humanitas Clinical and Research Center-IRCCSDepartment of Immunology and Inflammation, Humanitas Clinical and Research Center-IRCCSAbstract Background Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables. Methods Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected. Results In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4–63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036). Conclusions Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.http://link.springer.com/article/10.1186/s12967-020-02508-4Duodenal cancerTumor infiltrating cellsPrognosis |
| spellingShingle | G. Donisi G. Capretti N. Cortese A. Rigamonti F. Gavazzi G. Nappo A. Pulvirenti M. Sollai P. Spaggiari A. Zerbi F. Marchesi Immune infiltrating cells in duodenal cancers Journal of Translational Medicine Duodenal cancer Tumor infiltrating cells Prognosis |
| title | Immune infiltrating cells in duodenal cancers |
| title_full | Immune infiltrating cells in duodenal cancers |
| title_fullStr | Immune infiltrating cells in duodenal cancers |
| title_full_unstemmed | Immune infiltrating cells in duodenal cancers |
| title_short | Immune infiltrating cells in duodenal cancers |
| title_sort | immune infiltrating cells in duodenal cancers |
| topic | Duodenal cancer Tumor infiltrating cells Prognosis |
| url | http://link.springer.com/article/10.1186/s12967-020-02508-4 |
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