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

Abstract

BackgroundGallbladder 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.MethodsTumor 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.ResultsThe 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.ConclusionsDepending 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4147-6) contains supplementary material, which is available to authorized users.

T lymphocyte subsets in cancer immunity: Friends or foes

“…It was revealed that patients with poor response to CD3 stimulation exhibited a higher incidence of recurrent cancer . High numbers of CD8 + CTLs in the TME was associated with a better survival of the patients in bladder cancer as well . Interestingly, in this case, the CD8 + CTL to Treg ratio, within the TME, was also found to be associated to a favorable clinical response to neoadjuvant chemotherapy (NAC) .…”

“…High numbers of CD8 + CTLs in the TME was associated with a better survival of the patients in bladder cancer as well . Interestingly, in this case, the CD8 + CTL to Treg ratio, within the TME, was also found to be associated to a favorable clinical response to neoadjuvant chemotherapy (NAC) . This cell ratio could therefore be predictive of the response to NAC in bladder cancer and could help the management of the disease in advanced stages.…”

Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer

“…Likewise, a relationship between tumor-infiltrating immune cells and GBC prognosis has been suggested. In fact, recent published data from our and other groups showed that CD8 + T cell infiltration at different disease stages correlates with improved survival of GBC patients [ 22 – 24 ]. In one study, in which 45 tumor samples from GBC patients and 65 benign gallbladder tissues were examined, increased frequencies of CD4 + , CD8 + T cells and DCs were observed in GBC samples, which significantly correlated with prolonged patient survival [ 23 ].…”

“…In a more recent study, Oguro and coworkers [ 25 ] analyzed 211 GBC samples and found that a lower density of tumor-infiltrating CD8 + cells and higher ratios between Foxp3 + /CD4 + , B and T lymphocyte attenuator/CD8 + , and casitas-B-lineage lymphoma protein-b/CD8 + were significantly associated with shorter overall survival in GBC patients. Moreover, in a cohort of 80 Chilean GBC patients, we observed that a greater infiltration of CD8 + T cells in cancer tissue was associated with a favorable prognostic biomarker for both early and advanced stage patients [ 24 ]. Altogether, these observations strongly indicate that a natural host CD8 + T cell-mediated immune response against GBC increases patient survival.…”

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

“…Also, the heterogeneity in TME is associated with prognosis or drug response. For example, higher proportion of immune cells in the tumor microenvironment is associated with better survival [23][24][25] and better response to checkpoint blockade immunotherapies [26][27][28] . On the other hand, a higher proportion of stromal cells is associated with worse survival 29 , especially in GC [30][31][32] , and worse response to checkpoint blockade immunotherapies 33 .…”