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Treatment with activated autologous lymphocytes (AALs) has demonstrated mixed results for cancer treatment. Preliminary results revealed that the proportion of cluster of differentiation (CD)8 + CD57 + T cells is significantly increased in AALs, indicating that they are able to determine treatment outcome. Therefore, the role of CD8 + CD57 + T cells in AAL efficacy was investigated. T lymphocytes were isolated from 35 patients with stage IV gastric carcinomas (17 men and 18 women; aged 41-84 years) receiving immunotherapy using AALs (IAAL). Using fluorescence activated cell sorting, CD8, CD27, CD57, and forkhead box protein 3 (FOXP3) expression was investigated on CD8 + T cell populations in CD8 + T cell differentiation prior to and following in vitro culture. The association between these populations and progression-free survival (PFS) was analyzed using Cox univariate, and multivariate analyses and Kaplan-Meier survival analysis. CD57 expression was negative in early-differentiated CD8 + T cells (CD27 + CD8 + CD57 - ), and positive in intermediate- (CD27 + CD8 + CD57 + ) and terminal- (CD27 - CD8 + CD57 + ) differentiated CD8 + T cells. Univariate analysis revealed a significant association between terminal-CD8 + T cells and longer PFS times (P=0.035), whereas CD57 - FOXP3 + CD8 + T cells were associated with shorter PFS times. Multivariate analysis revealed that CD57 - FOXP3 + CD8 + T cells was an independent poor prognostic factor, whereas CD57 + FOXP3 + CD8 + T cells were not associated with PFS. Although IAAL increased the proportion of terminal-CD8 + T cells relative to the pre-culture proportions, patients with a high CD57 - FOXP3 + CD8 + T cell percentage exhibited repressed terminal-CD8 + T cell induction, leading to poor patient prognosis. Terminally differentiated CD27 - CD8 + CD57 + T cells were responsible for the effectiveness of AALs; however, CD57 - FOXP3 + CD8 + T cells abrogated their efficacy, possibly by inhibiting their induction.

oncology letters

Terminally differentiated CD8+ T cells and CD57‑FOXP3+CD8+ T cells are highly associated with the efficacy of immunotherapy using activated autologous lymphocytes