Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma

Li, Rutao; Huang, Xing; Yang, Wenmin; Wang, Jifan; Liang, Yantao; Zhang, Te; Mao, Qixing; Xia, Wenjie; Xu, Lin; Xu, Xinyu; Dong, Gaochao; Jiang, Feng

doi:10.1002/cjp2.281

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…58 Mature TLS rather than immature TLS was indicative of a better prognosis in ESCC patients. 59 To increase the detection accuracy rate of mature TLS, we used the expression of CD20 and CD8 which represented both the T cells and B plasma cells maturation combined with the formation of germinal cells to confirm the presence of TLS. The mature TLS presence rate was 37% in our analysis, which was lower than the 73% that was reported in the other literature.…”

Section: Discussionmentioning

confidence: 99%

“…The mature TLS presence rate was 37% in our analysis, which was lower than the 73% that was reported in the other literature. 59 Using different cell markers in immunohistochemistry to detect TLS may be the major reason. In addition, no significant correlation was displayed between the frequency of mature TLS and some clinicopathological parameters.…”

Section: Discussionmentioning

confidence: 99%

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Integrative analysis of tertiary lymphoid structures and immune microenvironment in patients with esophageal carcinoma

Yao

Xuan

Wang

et al. 2023

Tumori

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Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common upper gastrointestinal malignancies worldwide. Tertiary lymphoid structures (TLS) are tumor-infiltrating immune cells aggregates coupled with stromal cells which are similar to secondary lymphoid organs. The objective of this study is to explore the predictive effects of two common genes associated with TLS models on prognosis and immunotherapy effects in ESCC patients. Methods: Clinical information for ESCC patients in the TCGA(The Cancer Genome Altas) cohort and GSE 53625 were collected. All of the samples were classified as either high score group or low score group based on two TLS signatures, and the association between TLS signatures and survival, clinical indicators, genomic burden, stemness indices analysis, tumor microenvironment and immunotherapy response were performed. Furthermore, the mature TLS was also assessed in ESCC tissue microarray. Results: In our study, we quantified the score of TLS_9 and TLS_12, respectively, reflecting the different statuses of TLS (TLS_9 = B and T cells in TLSs; TLS_12 = neogenesis of TLSs). Subsequently, we explored the effect of TLS score on ESCC tumor microenvironment quantified by multiple algorithms. We found that a correlation analysis indicated that TLS_9 and TLS_12 were all positively correlated with CD8+ T cell, NK cells, CD4+ T cells, M1 macrophages and so on. Meanwhile, some cells present a different correlation pattern of TLS_9 and TLS_12, including activated CD4+ memory T cells and Tgd cells. Immune-related analysis revealed that the TLS_12 and TLS_9 scores were all positively correlated with immune dysfunction, yet negatively correlated with immune exclusion. Following this, the biological roles of TLS_9 and TLS_12 scores were investigated. Also, we noticed that the TLS score could significantly affect the CAFs infiltration and be associated with the genomic burden and tumor stemness. In addition, we explored the prognostic value of mature TLS through tissue microarray (TMA). Our result displayed ESCC patients with the presence of mature TLS had a better prognosis than ESCC patients without it. Conclusions: Our study indicated that ESCC patients with the presence of TLS had better outcomes and an inflamed immune microenvironment. In addition, both TLS-9 and TLS-12 gene signatures could be used as potential biomarkers for the immunotherapy of ESCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrative analysis of tertiary lymphoid structures and immune microenvironment in patients with esophageal carcinoma

Yao

Xuan

Wang

et al. 2023

Tumori

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“…Eight samples with high expression of TLSs were selected for multiplex immunohistochemistry (mIHC). The positive criteria for defining TLSs were: the simultaneous expression of labeled CD20, CD21, CD3, CD8, bcl6, and pnad in the cluster‐like structure of lymphocytes 18 . When CD20 and CD21 are highly expressed in the germinal centers of TLSs, they are mature TLSs 19 .…”

Section: Methodsmentioning

confidence: 99%

“…The positive criteria for defining TLSs were: the simultaneous expression of labeled CD20, CD21, CD3, CD8, bcl6, and pnad in the cluster-like structure of lymphocytes. 18 When CD20 and CD21 are highly expressed in the germinal centers of TLSs, they are mature TLSs. 19 All slices were evaluated by three pathologists (J.J., N.Z., and Y.L., 6 years, with 10 years and 25 years of experience) for the presence of TLSs under HE staining, and the tissue types were recorded.…”

Section: Histopathological Analysismentioning

confidence: 99%

Analysis of the Correlation and Prognostic Significance of Tertiary Lymphoid Structures in Breast Cancer: A Radiomics‐Clinical Integration Approach

et al. 2023

Magnetic Resonance Imaging

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BackgroundTertiary lymphoid structures (TLSs) are potential prognostic indicators. Radiomics may help reduce unnecessary invasive operations.PurposeTo analyze the association between TLSs and prognosis, and to establish a nomogram model to evaluate the expression of TLSs in breast cancer (BC) patients.Study TypeRetrospective.PopulationTwo hundred forty‐two patients with localized primary BC (confirmed by surgery) were divided into BC + TLS group (N = 122) and BC − TLS group (N = 120).Field Strength/Sequence3.0T; Caipirinha‐Dixon‐TWIST‐volume interpolated breath‐hold sequence for dynamic contrast‐enhanced (DCE) MRI and inversion‐recovery turbo spin echo sequence for T2‐weighted imaging (T2WI).AssessmentThree models for differentiating BC + TLS and BC − TLS were developed: 1) a clinical model, 2) a radiomics signature model, and 3) a combined clinical and radiomics (nomogram) model. The overall survival (OS), distant metastasis‐free survival (DMFS), and disease‐free survival (DFS) were compared to evaluate the prognostic value of TLSs.Statistical TestsLASSO algorithm and ANOVA were used to select highly correlated features. Clinical relevant variables were identified by multivariable logistic regression. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), and through decision curve analysis (DCA). The Kaplan–Meier method was used to calculate the survival rate.ResultsThe radiomics signature model (training: AUC 0.766; test: AUC 0.749) and the nomogram model (training: AUC 0.820; test: AUC 0.749) showed better validation performance than the clinical model. DCA showed that the nomogram model had a higher net benefit than the other models. The median follow‐up time was 52 months. While there was no significant difference in 3‐year OS (P = 0.22) between BC + TLS and BC − TLS patients, there were significant differences in 3‐year DFS and 3‐year DMFS between the two groups.Data ConclusionThe nomogram model performs well in distinguishing the presence or absence of TLS. BC + TLS patients had higher long‐term disease control rates and better prognoses than those without TLS.Evidence Level2Technical EfficacyStage 2

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“…GC is a dynamic region with a network of CD21 + /CD23 + FDC and B-cell lymphoma 6 protein (BCL6) + CD20 + B cells, primarily involved in B cell activation, proliferation, and differentiation during immune response ( 27 , 30 , 31 ). If the GC structure was clearly visible under HE, it was considered to be mature TLS ( 54 ); otherwise, it required to further identification of CD21 + /CD23 + FDC and BCL6 + CD20 + B cells in GC by IHC and IF ( Figure 2 ).…”

Section: Maturity Of Tlsmentioning

confidence: 99%

Tertiary lymphoid structures in cancer: maturation and induction

Chen,

Wu,

Yan

et al. 2024

Front. Immunol.

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Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumor-associated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value in various cancers. In recent years, the concept of maturity regarding TLS has been proposed and mature TLS, characterized by well-developed germinal centers, exhibits a more potent tumor-suppressive capacity with stronger significance. Meanwhile, more and more evidence showed that TLS can be induced by therapeutic interventions during cancer treatments. Thus, the evaluation of TLS maturity and the therapeutic interventions that induce its formation are critical issues in current TLS research. In this review, we aim to provide a comprehensive summary of the existing classifications for TLS maturity and therapeutic strategies capable of inducing its formation in tumors.

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Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma

Cited by 12 publications

References 29 publications

Integrative analysis of tertiary lymphoid structures and immune microenvironment in patients with esophageal carcinoma

Integrative analysis of tertiary lymphoid structures and immune microenvironment in patients with esophageal carcinoma

Analysis of the Correlation and Prognostic Significance of Tertiary Lymphoid Structures in Breast Cancer: A Radiomics‐Clinical Integration Approach

Tertiary lymphoid structures in cancer: maturation and induction

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