Abstract
The existence of intratumoral tertiary lymphoid structure (iTLS) has been reported to correlative with favorable clinical outcomes for patients with hepatocellular carcinoma (HCC). However, little is known about the role of peritumoral TLS (pTLS). This study aimed to investigate the prognostic role of pTLS either alone or jointly with iTLS and the potential association with local immune response in HCC. The formation and cellular composition of TLS was evaluated by hematoxylin & eosin and immunohistochemistry. Evaluation of tumor-infiltrating immune cells and formation of germinal center (GC) inside TLS was performed by immunohistochemistry. The gene expression profiles were analyzed by real-time PCR. In a total of 360 patients from two independent cohorts, the pTLS was identified in most, whereas iTLS could be observed in only approximately 30% of HCC specimens. Patients with high pTLS densities were associated with improved outcomes, those present with characteristic morphology of GC, particularly, showing an even better prognosis. The combination of pTLS and iTLS allowed the identification of patients with best prognosis. Tumors with high pTLS density showed significantly increased expression of Th1-, Th17- and immune suppression-related genes, as well as significantly higher infiltration of CD3+, CD8+ and CD20+ cells and lower infiltration of FOXP3+, CD68+ and PD1+ cells. Conclusively, we provide evidence that pTLS is associated with intratumoral immune infiltration, highlighting the dynamic interplay between pTLS and immune cells recruitment. High pTLS density links to a tumor microenvironment with an active immune reaction and improved patient survival and represents a promising prognostic biomarker for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common human cancer, causing for the fourth most cancer-related mortality globally [1]
tertiary lymphoid structure (TLS) was found within tumor tissue or peritumoral region or distant normal liver parenchymal (Figure 1A). intratumoral tertiary lymphoid structure (iTLS) presented in 76 (31.7%) tumors, whereas peritumoral TLS (pTLS) were detected in tumor periphery of 228 (95%) patients (Figures 1B, C)
We examined the presence of iTLS relative to pTLS density and found a higher pTLS density in cases presence of iTLS (Figure 1D)
Summary
Hepatocellular carcinoma (HCC) is the sixth most common human cancer, causing for the fourth most cancer-related mortality globally [1]. Tumor-associated TLS, characterized by B cell lymphoid follicles with or without germinal centers, T cell-rich zones, and specialized vessels known as high endothelial venules (HEVs), provide necessary specialized vasculature and chemoattractant, allowing for immune cells infiltration [10, 11]. Accumulating evidence have shown that the presence of TLS, whether in tumor core or peritumoral areas, correlated with favorable clinical outcomes in various cancers, including breast cancer, colorectal cancer and lung cancer, and tumor-infiltrating immune cells [5, 16, 17]. Finkin et al demonstrated that TLSs located in the non-tumoral liver tissue served as niches for malignant hepatocyte progenitors and correlated with an elevated risk of late HCC recurrence [18]. We investigated the presence of iTLS in HCC tissues and their correlation with clinical outcomes, and found the presence of iTLS correlated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
