LAG3 as a marker of immune activation in esophageal squamous carcinoma treated with concurrent chemoradiotherapy

Esophageal squamous carcinoma (ESCC) is a common malignant tumor of the gastrointestinal tract with high morbidity and mortality rates. Lymphocyte activation gene-3 (LAG3), an important suppressive immune checkpoint in tumor immunity, exhibits a wobbling effect in the prediction of ESCC efficacy.

Tumor bite paraffin-embedded specimens from 84 patients diagnosed with ESCC, all of whom received radical concurrent chemoradiotherapy (CCRT) at our institution, were screened. For each tissue, we delineated the partitions and analyzed the spatial distribution of the tumor in an in situ immune microenvironment. The density and regional characteristics of immune factor-positive cells, together with the dynamics of various cells based on treatment regimens, were considered important factors influencing the prognostic significance of cancer.

Compared with baseline tissues, the density of CD4 + and CD8 + T cells in the tumor microenvironment of the on-treatment tissues decreased, but the expression of IFN-γ in CD4 + and CD8 + T cells increased. The density of LAG3 positive cells was correlated significantly with the density of CD4 + and CD8 + T cells in both baseline and on-treatment tissues. The density of LAG3 + T cells and the rate of LAG3 positivity in activated CD4 + and CD8 + T cells were associated with elevated Ki67 expression. There was a significant correlation between high LAG3 expression and active CD4 + and CD8 + T cells in tumor cells. Elevated densities and tighter spatial relationships of both CD4 + and CD8 + T cells were associated with longer overall survival with ESCC.

Concurrent chemoradiotherapy without combined immunotherapy inhibited tumor-infiltrating T cells to a certain extent, and elevated immune checkpoint LAG3 was closely associated with immune activation in the ESCC tumor microenvironment.