Tertiary lymphoid structures show infiltration of effective tumor-resident T cells in gastric cancer

Abstract

Several studies have reported that tissue-resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103⁺ T cells and to assess the association between CD103⁺ T cells and TLSs. CD103⁺ T cells were observed in the tumor epithelium accompanied by CD8⁺ T cells and were associated with a better prognosis in GC. Furthermore, CD103⁺ T cells were located around TLSs, and patients with CD103^high had more rich TLSs. Patients who had both CD103^high cells and who were TLS-rich had a better prognosis than patients with CD103^low cells and who were TLS-poor. Moreover, for patients who received PD-1 blockade therapy, CD103^high and TLS-rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103⁺ CD8⁺ T cells and showed that CD103⁺ CD8⁺ T cells in GC expressed higher levels of PD-1, granzyme B, and interferon-γ than CD103^- CD8⁺ T cells. Our results suggested that CD103⁺ CD8⁺ cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.

Keywords: CD103; antitumor immunity; gastric cancer; tertiary lymphoid structure; tissue-resident memory T cell.