Oral cancer-associated tertiary lymphoid structures: gene expression profile and prognostic value

Abstract

Summary Tertiary lymphoid structure (TLS) provides a local and critical microenvironment for both cellular and humoral immunity and supports effective antigen presentation and lymphocyte activation. However, the gene expression profile and prognostic significance of TLS in oral cancer remain largely unrevealed. In this study, we found the presence of both intratumoral and peritumoral TLSs in a series of 65 patients with oral cancer treated by surgical resection, with positive detection rates of 33.8 and 75.4%, respectively. The presence of intratumoral TLSs, but not peritumoral TLSs, was significantly associated with decreased P53 and Ki67 scores (P = 0·027 and 0·047, respectively). The survival analyses revealed that oral cancer patients with higher grades of TLSs was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·037 and 0·031, respectively). Gene expression profiling analysis of the cytokines and chemokines responsible for lymph-node neogenesis identified a three-up-regulated-gene set, i.e. IL7, LTB and CXCL13, which was shown to be correlated with human oral cancer-associated TLSs. This study provides a framework for better understanding of oral cancer-associated TLSs and for delineating future innovative prognostic biomarkers and immune therapeutic strategies for oral cancer.

Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma

“…For OSCC, a previous study adopted CD3 and CD20 as the core markers, while another study added CD21 as the marker of follicular DCs in the TLS. 19,38 In the present study, we adopted PNAd, the specific marker for HEV, as the core marker in the TLS. HEVs, defined as the specific vessels in lymph nodes, are critical for the formation of TLSs and recruitment of naive B cells and T cells from blood to lymphatic tissues through bonding to L-selectin on the surface of naive lymphocytes and activation of B cells and T cells, which might help eliminate tumours.…”

B cells and cancer: To B or not to B?

“…A high density of B cell follicles correlated with longer progression-free survival (PFS) and OS in NSCLC ( Germain et al, 2014 ). The presence of TLSs was reported in many cancer types, including melanoma ( Ladányi et al, 2007 ), bladder ( Zirakzadeh et al, 2020 ), colorectal ( Di Caro et al, 2014 ; Posch et al, 2017 ), gastric ( Yamakoshi et al, 2020 ), gastrointestinal stromal tumor ( Lin et al, 2020 ), HCC ( Li et al, 2020a ; Calderaro et al, 2019 ) ovarian ( Kroeger et al, 2016 ), oral ( Li et al, 2020b ), squamous lung ( Siliņa et al, 2018 ), and pancreatic carcinomas ( Hiraoka et al, 2015 ; Table 1 and Fig. 1 ; reviewed in Sautès-Fridman et al, 2019 ).…”

Tumor-Infiltrating CD20+ B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment

“…These structures have been associated with positive prognostic value in some tumors [ 55 , 56 ], such as high-grade serous ovarian cancer, where tumor infiltration by CD8 + T cells only showed prognostic value when it was combined with the presence of TLS and a high count of plasma cells, CD4 + T cells and CD20 + B cells [ 56 ]. In oral cancer, higher grades of TLS have also been associated with improved survival [ 57 ]; however, good and poor clinical outcomes have been correlated with different cellular components of TLS, such as dendritic cells, B cells, and different subsets of T cells [ 58 ]. This suggests that the cellular components of TLS affect the antitumor immune response in different cancer types, such as gastric cancer, where a high number of CD20 + B cells within lymphoid aggregates was an independent predictor of good prognosis [ 59 ].…”