Objective To investigate lymphocyte interstitial infiltration condition and the changes of immune checkpoint gene expression in different stages of early esophageal cancer.

Methods A retrospective analysis was conducted on the clinical data of 90 patients with early esophageal cancer. Based on the pathological depth of infiltration, they were divided into three types: T1a-M1, T1a-M2, and T1a-M3, with 30 cases in each type. Additionally, 30 cases of paired normal mucosa tissues adjacent to the cancer were selected. Hematoxylin-eosin (HE) staining was used to observe tissue morphology. Immunohistochemistry was employed to detect the expression of CD3, CD4, CD8, and CD20. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was applied to measure the mRNA expression levels of immune checkpoint genes programmed death ligand-1 ( PD-L1 ), cytotoxic T-lymphocyte-associated protein 4 ( CTLA4 ), T-cell immunoglobulin and mucin domain-3 ( TIM-3 ), lymphocyte activation gene 3 ( LAG3 ), programmed death receptor-1 ( PD-1 ), programmed death ligand-2 ( PD-L2 ), and T-cell immunoreceptor with Ig and ITIM domains protein (TIGIT).

Results As the stage of early esophageal cancer progressed, the ratio of tumor cells to lymphocytes increased. The number of CD3⁺ T cells was greater than that of CD20⁺ B cells, and the proportion of CD4⁺ T cells among total T cells was higher than that of CD8⁺ T cells (P < 0.001). The mRNA expression levels of gene in immune checkpoints in patients were elevated (P < 0.05). Compared with normal adjacent tissues, the expression levels of PD-L1 mRNA, CTLA4 mRNA, TIM-3 mRNA, PD-1 mRNA, and TIGIT mRNA were elevated in patients with T1a-M1, T1a-M2, and T1a-M3 types (P < 0.05). Compared with normal adjacent tissues, the expression levels of LAG3 mRNA and PD-L2 mRNA were increased in patients with T1a-M2 and T1a-M3 types (P < 0.05).

Conclusion The progression of early esophageal cancer staging is correlated with increased immune checkpoint gene expression and a decreased lymphocyte ratio, suggesting that changes in the immune microenvironment may be involved in tumor progression.