The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

Yu, Ji-Shang; Huang, WeiBin; Zhang, Yuhui; Chen, Jian; Li, Jin; Fu, Huafeng; Wei, Zhe-Wei; He, Yong

doi:10.4149/neo_2022_220128n123

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…Furthermore, several studies demonstrated that the abundance of intratumor TLSs was associated with gene mutation, including BRAF. 45 46 In contrast, our study showed that common mutated genes in CRCLM, including BRAF and NRAS, have no significant association with intratumor and peritumor TLSs, which may have resulted from the different types of cancer. While intratumor and peritumor TLSs were clear prognostic indicator in this study, the standard methods for quantifying and characterizing them are highly labor intensive and pathologist-dependent.…”

Section: Discussioncontrasting

confidence: 80%

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Zhang

Wang

Zuo

et al. 2023

J Immunother Cancer

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BackgroundTertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).Methods603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.ResultsT score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.ConclusionsThe distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

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Section: Discussioncontrasting

confidence: 80%

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Zhang

Wang

Zuo

et al. 2023

J Immunother Cancer

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“…1 ), 106 records were identified from public databases in the initial literature search. After carefully screening titles and abstracts, and subsequent full-text review, 11 studies incorporating 4224 GC samples were ultimately enrolled (Yu et al 2022 ; Li et al 2020 ; Yin et al 2022 ; Jiang et al 2022 ; Li et al 2023 ; Kemi et al 2023 ; Mori et al 2022 ; Cheng et al 2021 ; Mori et al 2021 ; Yamakoshi et al 2021 ; He et al 2020 ). Baseline information and major characteristics are shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Proteomic markers such as PD-L1 expression (Kim et al 2018 ) and molecular markers such as microsatellite instability (MSI) (Kwon et al 2021 ) have been established as potential biomarkers of prognosis and responses to immune checkpoint inhibitors (ICIs), whereas findings between different clinical trials were inconsistent. Recently, components in the tumor microenvironment (TME) of GC, such as the contents (Ren et al 2021 ) and spatial location (Chen et al 2022 ) of different cell types, and specialized structures like tertiary lymphoid structure (TLS) (Yu et al 2022 ), have received increasing attention for they could affect prognosis and immunotherapy efficiency.…”

Section: Introductionmentioning

confidence: 99%

Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies

Peng,

Wu,

Zhang

et al. 2024

J Cancer Res Clin Oncol

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Background The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain. Methods A systematic search was performed in public databases for eligible studies as of April 2, 2023. Meta-analyses were performed to interrogate the associations between TLS levels and prognosis and immunotherapy response of GC. Bioinformatic analyses based on the nine-gene signature of TLS were further conducted to capture the biological underpinnings. Results Eleven studies containing 4224 GC cases were enrolled in the meta-analysis. TLS levels positively correlated with smaller tumor size, earlier T stage and N stage. Moreover, higher TLS levels were detected in diffuse and mix subtypes of GC (P < 0.001). Higher TLS levels strongly predicted favorable postoperative overall survival of GC, with HR of 0.36 (95%CI 0.26–0.50, P < 0.001) and 0.55 (95%CI 0.45–0.68, P < 0.001) of univariate and multivariate Cox analysis, respectively. Higher TLS levels were also in favor of the treatment response of anti-PD-1 inhibitors as later-line therapy of GC. TLS levels positively correlated with immune effector cells infiltration, diversity and richness of T cell receptor and B cell receptor repertoire, immune checkpoint genes expression, and immune-related genes mutation of GC in the TCGA-STAD cohort, representing higher immunogenicity and immunoactivity. Moreover, moderate accuracy of TLS levels in predicting benefit from anti-PD-1 inhibitors in the PRJEB25780 cohort was also validated (AUC 0.758, 95%CI 0.583–0.933), higher than the microsatellite instability-score and Epstein-Barr virus status. Conclusions TLS levels demonstrated potential in predicting the postoperative prognosis and immunotherapy response of GC.

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“…Overall, TLSs have a bivalent influence on host–tumor interactions, and they are found in almost all solid tumors. Studies have shown that TLSs indicate a favorable prognosis for most human tumors, including breast cancer [ 12 ], lung adenocarcinoma (LUAD) [ 13 ], hepatocellular carcinoma [ 14 ], colorectal cancer [ 15 ], cutaneous squamous cell carcinoma [ 16 ], gastric cancer [ 17 ], cervical cancer [ 18 ], and oral cancer [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Immature central tumor tertiary lymphoid structures are associated with better prognosis in non-small cell lung cancer

Xiaoxu,

Min,

Chengcheng

2024

BMC Pulm Med

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Background & aims Tertiary lymphoid structures (TLSs) are predictive biomarkers of favorable clinical outcomes and immunotherapy response in several solid malignancies, including non-small cell lung cancer (NSCLC). However, the relationship between TLSs and NSCLC prognosis has not been eludicated from the aspects of location, density, and maturity. This study aimed to investigate the clinicopathological and prognostic significance of TLSs in NSCLC. Methods A collection of 151 resected pulmonary nodules in patients with NSCLC was retrospectively analyzed. Two experienced pathologists reviewed hematoxylin-eosin (H&E) slides and assessed TLS scores at different anatomic subregions. Then, we analyzed their correlation with clinicopathologic parameters and CD8 staining intensity and assessed multiple clinicopathological factors affecting patient prognosis. Results CD8 expression was correlated with total (TLS-CT) (P = 0.000), aggregates (Agg) (TLS-CT) (P = 0.001), follicles (FOL)-I (TLS-CT) (P = 0.025), and TLS(overall) (P = 0.013). TLS scores in the central tumor (CT) and invasion margin (IM) areas were negatively correlated with distant metastasis and Union for International Cancer Control (UICC) stage in NSCLC patients, while TLS score in the CT area was positively correlated with CD8 expression. TLS (overall), Agg (TLS-CT), and FOL-I (TLS-CT) were positively correlated with distant metastasis, UICC stage, and CD8 expression in NSCLC patients. Agg (TLS-IM) was positively correlated with distant metastasis and UICC stage. FOL-I (TLS-IM) was positively correlated with UICC stage. FOL-II (TLS-IM) was positively correlated with distant metastasis (P < 0.05). Multivariate Cox regression analysis showed that unfavorable independent prognostic factors were associated with metastasis status and UICC stage. Independent prognostic factors with protective effects included Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS (P < 0.05). Conclusion Histological score assessment of H&E sections of Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS levels in NSCLC has prognostic value.

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The association of immune cell infiltration and prognostic value of tertiary lymphoid structures in gastric cancer

Cited by 13 publications

References 23 publications

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies

Immature central tumor tertiary lymphoid structures are associated with better prognosis in non-small cell lung cancer

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