Circulating CD8⁺CD28^- suppressor T cells tied to poorer prognosis among metastatic breast cancer patients receiving adoptive T-cell therapy: A cohort study.

Abstract

This study aimed to determine the prognostic value of circulating CD8⁺CD28^- T lymphocytes among breast cancer patients treated with adoptive T-lymphocyte immunotherapy after chemotherapy. Two hundred and thirty-two breast cancer patients underwent adoptive T-cell immunotherapy. Circulating CD8⁺CD28^- proportion was measured by flow cytometry. Median proportion of CD8⁺CD28^- was 24.2% and set as the categorical cutoff value for further analysis. The median survival was estimated by Kaplan-Meier curve, with difference detection and hazard ratio estimation by log-rank test and Cox hazard proportion regression model. With adoptive T-cell therapy, patients with higher CD8⁺CD28^- levels experienced median progression-free and overall survival of 7.1 months and 26.9 months, respectively-significantly shorter than patients with lower levels (11.8 and 36.2 months). CD8⁺CD28^- proportion >24.2% demonstrated a hazard ratio (HR) of 2.06 (95% confidence interval [CI] 1.31-3.12) for progression and an HR of 1.97 (95% CI 1.06-3.67) for death. Among patients who had received previous first-line chemotherapy, CD8⁺CD28^- proportion >24.2% demonstrated an HR of 2.66 (95% CI 1.45-4.88) for progression. Among patients exposed to previous second-line or higher chemotherapy, CD8⁺CD28^- proportion >24.2% demonstrated a 486% higher risk for death (HR = 5.86, 95% CI 1.77-19.39). A 1% increase in suppressive T cells was associated with a 5% increased risk of death. Elevated peripheral blood CD8⁺CD28^- was associated with poorer prognosis for metastatic breast cancer, especially for higher risk of progression among patients with first-line chemotherapy and higher risk of death among patients with more than second-line chemotherapy.