Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

Abstract

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors. Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors. Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 -0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 -0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 -0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer. Conclusion:High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.

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

“…In terms of clinical characteristics, Zhao et al 37 showed by a meta‐analysis that TLSs expression correlated with tumor volume and clinical stage. However, our study found no significant differences between tumor size, margin, TIC, number of lesions, and TLSs expression.…”

Tumor-Infiltrating B Lymphocytes: Promising Immunotherapeutic Targets for Primary Liver Cancer Treatment

“…B cells produce cytokines that can facilitate TLS formation at sites of chronic inflammation [ 78 ]. Several pieces of evidence indicate that TLSs play a major role in controlling tumor progression and they are related to better clinical outcomes in both human disease and mouse models [ 54 , 76 ]; for this reason, TLS structures are considered as prognostic markers predicting longer patient survival [ 79 , 80 ]. Thus, TLSs may represent the initiation of a local antitumor B-cell-mediated immunity.…”

“…Considering the B-cell ability to release cytokines, B lymphocytes also recruit other immune cells to TLSs and effector sites and induce the antitumor cytolytic T-cell activity through the interaction between CD27-expressing B cells and CD70-expressing CD8+ T lymphocytes [ 81 , 82 ]. Tumor-associated TLSs may be the place where B cells undergo cell clonal amplification, somatic hypermutation, and class-switch recombination, revealing a local antigen-driven response and antibody affinity maturation [ 49 , 79 ]. Thus, B cells differentiate into plasma cells producing significant amounts of tumor-specific antibodies, or presenting tumor-derived peptides to T cells, modulating their phenotypes [ 54 ].…”

Tertiary Lymphoid Structures: A Potential Biomarker for Anti-Cancer Therapy

“…In patients with lung squamous cell carcinoma who received neoadjuvant chemotherapy, the density of TLSs in tumors became similar, losing its predictive effect [ 27 ]. The high TLS density in tumors is usually associated with high TIL density as well as with the expression of PD-1/PD-L1, suggesting the potential benefit from immunotherapies [ 37 , 38 ]. However, it was found that a subtype of glioma with high immune infiltrations and TLSs resulted in poor prognosis.…”