High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival

Abstract

Background: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages.

Methods: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3(+), CD4(+), CD8(+), and Foxp3(+) T cell populations, and the results were associated with clinical stage and patient survival.

Results: The majority of tumor samples showed CD3(+) T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8(+), but not CD4(+), T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4(+)/CD8(+) T cell ratio was related with increased survival. Additionally, the presence of Foxp3(+) T cells correlated with decreased patient survival, whereas a <= 1 Foxp3(+)/CD8(+) T cell ratio was associated with improved patient survival.

Conclusions: Depending on the disease stage, the presence of CD8(+) and absence of Foxp3(+) T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy.