Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma
Ectopic lymphoid structures termed tertiary lymphoid structures (TLSs) have an immunomodulatory function and positively affect prognosis in certain cancers. However, their clinical relevance and prognostic utility in perihilar cholangiocarcinoma (pCCA) are unknown. Therefore, determining the involve...
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6107 |
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| author | Fa-Peng Zhang Ke Zhu Tai-Feng Zhu Chao-Qun Liu Hong-Hua Zhang Lei-Bo Xu Gang Xiao Chao Liu |
| author_facet | Fa-Peng Zhang Ke Zhu Tai-Feng Zhu Chao-Qun Liu Hong-Hua Zhang Lei-Bo Xu Gang Xiao Chao Liu |
| author_sort | Fa-Peng Zhang |
| collection | DOAJ |
| description | Ectopic lymphoid structures termed tertiary lymphoid structures (TLSs) have an immunomodulatory function and positively affect prognosis in certain cancers. However, their clinical relevance and prognostic utility in perihilar cholangiocarcinoma (pCCA) are unknown. Therefore, determining the involvement and prognostic utility of TLSs in pCCA is the aim of this study. Ninety-three patients with surgically resected pCCA were included retrospectively. Hematoxylin and eosin and immunohistochemical staining identified and classified the TLSs, and multiplex immunofluorescence determined the TLS composition in the pCCA sample. The correlations between clinical features and TLSs were analyzed using either Fisher’s exact test or the Chi-squared test. Recurrence-free survival (RFS) and overall survival (OS) correlations with TLSs were analyzed using Cox regression and Kaplan–Meier analyses. We identified TLSs in 86% of patients with pCCA, including lymphoid aggregates (6.45%), primary (13.98%) and secondary follicles (65.59%). Patients with intra-tumoral secondary follicle-like TLSs (S-TLSs) had better OS (<i>p</i> = 0.003) and RFS (<i>p</i> = 0.0313). The multivariate analysis identified the presence of S-TLSs as a good independent prognostic indicator for OS but not for RFS. Interestingly, the presence of S-TLS only indicated better 5-year OS in 54 patients without lymph node metastasis (LNM<sup>−</sup>, <i>p</i> = 0.0232) but not in the 39 patients with lymph node metastasis (LNM<sup>+</sup>, <i>p</i> = 0.1244). Intra-tumoral S-TLSs predicted longer OS in patients with surgically resected pCCA, suggesting intra-tumoral S-TLSs’ contribution to effective antitumor immunity and that S-TLSs hold promise for diagnostic and therapeutic development in pCCA. |
| first_indexed | 2024-03-09T17:14:19Z |
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| language | English |
| last_indexed | 2024-03-09T17:14:19Z |
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| series | Cancers |
| spelling | doaj.art-5ea8552d7faa4801b7a1eaa1041be2122023-11-24T13:46:18ZengMDPI AGCancers2072-66942022-12-011424610710.3390/cancers14246107Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar CholangiocarcinomaFa-Peng Zhang0Ke Zhu1Tai-Feng Zhu2Chao-Qun Liu3Hong-Hua Zhang4Lei-Bo Xu5Gang Xiao6Chao Liu7Department of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Biliary-Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaEctopic lymphoid structures termed tertiary lymphoid structures (TLSs) have an immunomodulatory function and positively affect prognosis in certain cancers. However, their clinical relevance and prognostic utility in perihilar cholangiocarcinoma (pCCA) are unknown. Therefore, determining the involvement and prognostic utility of TLSs in pCCA is the aim of this study. Ninety-three patients with surgically resected pCCA were included retrospectively. Hematoxylin and eosin and immunohistochemical staining identified and classified the TLSs, and multiplex immunofluorescence determined the TLS composition in the pCCA sample. The correlations between clinical features and TLSs were analyzed using either Fisher’s exact test or the Chi-squared test. Recurrence-free survival (RFS) and overall survival (OS) correlations with TLSs were analyzed using Cox regression and Kaplan–Meier analyses. We identified TLSs in 86% of patients with pCCA, including lymphoid aggregates (6.45%), primary (13.98%) and secondary follicles (65.59%). Patients with intra-tumoral secondary follicle-like TLSs (S-TLSs) had better OS (<i>p</i> = 0.003) and RFS (<i>p</i> = 0.0313). The multivariate analysis identified the presence of S-TLSs as a good independent prognostic indicator for OS but not for RFS. Interestingly, the presence of S-TLS only indicated better 5-year OS in 54 patients without lymph node metastasis (LNM<sup>−</sup>, <i>p</i> = 0.0232) but not in the 39 patients with lymph node metastasis (LNM<sup>+</sup>, <i>p</i> = 0.1244). Intra-tumoral S-TLSs predicted longer OS in patients with surgically resected pCCA, suggesting intra-tumoral S-TLSs’ contribution to effective antitumor immunity and that S-TLSs hold promise for diagnostic and therapeutic development in pCCA.https://www.mdpi.com/2072-6694/14/24/6107perihilar cholangiocarcinomatertiary lymphoid structuresoverall survivalrecurrenceimmunity |
| spellingShingle | Fa-Peng Zhang Ke Zhu Tai-Feng Zhu Chao-Qun Liu Hong-Hua Zhang Lei-Bo Xu Gang Xiao Chao Liu Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma Cancers perihilar cholangiocarcinoma tertiary lymphoid structures overall survival recurrence immunity |
| title | Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma |
| title_full | Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma |
| title_fullStr | Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma |
| title_full_unstemmed | Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma |
| title_short | Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma |
| title_sort | intra tumoral secondary follicle like tertiary lymphoid structures are associated with a superior prognosis of overall survival of perihilar cholangiocarcinoma |
| topic | perihilar cholangiocarcinoma tertiary lymphoid structures overall survival recurrence immunity |
| url | https://www.mdpi.com/2072-6694/14/24/6107 |
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