Tertiary lymphoid structures in head and neck squamous cell carcinoma improve prognosis by recruiting CD8+ T cells

Abstract

Tertiary lymphoid structures (TLSs) are formed in long-term chronic inflammation, promoting the local recruitment of lymphocytes, antigen presentation and regulation of immune response, correlated with a better prognosis for cancer patients. Although studies have been conducted to explore methods that accelerate the establishment of TLSs, related research in head and neck squamous cell carcinoma (HNSCC) is still lacking. In this study, we analysed data from The Cancer Genome Atlas and performed immunohistochemical staining analyses of 188 patient samples. The results showed that TLSs promoted the infiltration of immune cells. Patients with TLSs with high infiltration of CD8⁺ cells showed the best prognosis. Since lymphotoxin α (LTα) was significantly increased in tissues with TLSs, we overexpressed LTα in SCC7 cells (a mouse-derived HNSCC cell line) and established tongue-tumour-bearing models. The polychromatic observation of tissue sections showed that T-cell aggregation increased in the LTα cell group, and a grade 1 TLS was formed on the 12th day after inoculating the cells. Moreover, the tumour volume in the LTα group was significantly less than that of the control group, whereas both the number and the proportion of infiltrated CD8⁺ T cells were increased. The peripheral CD8⁺ cells in mice were removed, and no difference was observed in tumour size or TLS formation. Remarkably, we found that TLS led to an increase in the antitumour effect by recruiting CD8⁺ T cells in HNSCC, showing a CD8⁺ T-cell-dependent antitumour effect. Moreover, LTα overexpression in the tumour promoted the formation of TLSs.

Keywords: CD8+ T cells; head and neck squamous cell carcinoma; lymphotoxin α; tertiary lymphoid structure; tumour microenvironment.