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

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.