Research Paper Volume 12, Issue 4 pp 3451—3472
Existence of intratumoral tertiary lymphoid structures is associated with immune cells infiltration and predicts better prognosis in early-stage hepatocellular carcinoma
- 1 Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu 610041, China
- 2 Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- 3 Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510006, China
received: November 5, 2019 ; accepted: January 27, 2020 ; published: February 22, 2020 ;https://doi.org/10.18632/aging.102821
How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Tumor-associated tertiary lymphoid structures (TLS) play a critical role in the progression of various tumors. However, the dynamics of lymphocyte recruitment during hepatocellular carcinoma (HCC) clinical progression have not been fully elucidated. In the present study, tissue microarrays and hematoxylin-eosin staining were used to evaluate the existence and degree of TLS in HCC patients. Nine immune biomarkers in intratumoral tissues were examined by immunohistochemical staining. A total of 462 patients were recruited for the study. Kaplan–Meier analysis showed that TLS was inversely correlated with the risk of early tumor recurrence (P=0.014), whereas no association was found between TLS and overall survival. Cox regression analysis identified TLS as an independent prognostic factor for early HCC recurrence (P=0.005). In addition, TLS was associated with increased intratumoral CD3+, CD8+, CD20+, and decreased infiltration of Foxp3+ and CD68+ cells. A lower density of PD1+, TIM3+, and LAG3+ were found in TLS+ cases. Sub-analysis revealed the prognostic value of TLS on early-stage HCC (BCLC 0-A, TNM stage I-II) and HCC with solitary nodule. The validation cohort verified the prognostic value of TLS in early-stage HCC patients. These results suggest that TLS-targeted immune-modulating therapies may be a potential strategy for effective immune-mediated tumor suppression.