Prognostic impact of tertiary lymphoid structures in breast cancer prognosis: a systematic review and meta-analysis

Abstract

Background Tertiary lymphoid structures (TLSs), organizationally resemble lymph nodes, are frequently present in breast cancer (BCa). It is usually, but not always, associated with a positive prognosis or immunotherapy response in cancer patients. This meta-analysis was performed to assess the prognostic and clinical impact of TLSs in BCa. Methods We conducted a systematic search in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang Database to obtain eligible research data up to May 30, 2021. This meta-analysis is focusing on the studies evaluated the prognostic value of TLSs and the associated clinicopathologic indicators, related gene expression and survival. STATA software 16.0 software was used to assess the prognostic significance and clinical impact of TLSs. Results Nine studies involved with 2281 cases were incorporated in this meta-analysis, in which four of them evaluated the prognostic value of TLSs. There are 6 studies assessed the relationship of TLSs and 4 studies investigated the clinicopathologic parameters as well as the key gene expression, respectively. The results showed the presence of TLSs were predicting a better OS (HR = 0.61, 95% CI: 0.51–0.73, p < 0.001) and DFS (HR = 0.40, 95% CI: 0.17–0.93, p < 0.001) of BCa patients. It also revealed that the presence of TLSs was significantly correlated with tumor differentiation (p < 0.001), pTNM stage (p < 0.001), lymph node metastasis (p < 0.001), and TILs density (p < 0.001) of BCa, and the expression of Her2 (p < 0.001), ER (p < 0.001), PR (p < 0.001) and Ki67 (p = 0.009) of the tumor cell. Conclusion Our results indicated that high levels of TLSs could predict a favorable prognosis for BCa. Moreover, the TLSs were significantly correlated with the clinicopathological indicators and the critical gene expression of BCa, indicating its potential clinical impact on BCa patients.

NOS2 and COX2 Blockade Limits TNBC Disease Progression and Alters CD8+T Cell Spatial Orientation and Density

“…A layered effect was observed, reminiscent of an “Inside-out lymph node” consisting of cytolytic CD8 + T cells surrounded by separate layers of CD4 + T cells and B cells. Recently, tertiary lymphoid structures (TLS) have been detected in tumors, which correlate with improved survival (40, 41). This configuration suggests an orthogonality in the lymphoid population that is like lymph node structures.…”

The Presence of Tertiary Lymphoid Structures Provides New Insight Into the Clinicopathological Features and Prognosis of Patients With Breast Cancer

“…Although a previous meta-analysis by Zhang et al. suggested that TLSs were related to better prognosis, their result was based on a limited number of studies, with only two or three studies providing survival outcomes ( 9 ). Furthermore, all included studies in their meta-analysis showed that TLSs were beneficial for prognosis, but opposite conclusions have been reported in the recent study ( 10 ).…”

Immunological Landscape of HER-2 Positive Breast Cancer

“…Finally, a meta-analysis assessed the prognostic value of TLSs and their correlation with clinicopathological features, gene expression, and survival in all BC subtypes. A higher density of TLSs was reported to be significantly correlated with better DFS in all subtypes (HR = 0.40, 95% CI: 0.17−0.93, p < 0.001) [56].…”