Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer

Abstract

Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient's prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3 + Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.

Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

“…While the presence of TLS often positively impacts clinical outcomes, TLS composition itself might dictate treatment efficacy, tumor recurrence and patient survival. Indeed, Yamaguchi and colleagues 156 classified TLS into five categories based on their immune cell composition and found that TLS enriched in helper T cells were associated with disease relapse in advanced colorectal cancer. Another example is the diversity found among ASC where IgA producing cells are almost exclusively associated with a poor prognosis, while IgG + secreting cells frequently correlated with increased patient survival.…”

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

“…A large number of studies demonstrated that the tumor microenvironment is closely related to the prognosis and effectiveness of immunotherapy [45][46][47]. TLS is a crucial component of tumor immune microenvironment [5,48], which not only facilitating the recruitment of immune cells or play an anti-tumor role, but also act as a predictor for the prognosis of various cancer [4,7,10,15,22,24,34,39]. However, several studies reported the effect of TLS expression on prognosis and clinicopathological characteristics of solid tumor patient remains controversial [9,11,13,15].…”

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

“…B cells could be involved in the formation of TLS by producing CXCL13 and lymphotoxin [ 50 , 52 ], and also in the maturation of an antitumoral humoral response in the TME [ 50 ]. TLS have been reported in various types of cancers including lung, breast, pancreas, colorectal, and oral cancer [ 53 , 54 ]. 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 ].…”