Chemotherapy to induce T-cell subpopulation changes in advanced breast cancer patients

e12562 Background: Recent data suggest that some anti-cancer agents may generate a stimulation of the immune system that can account for additional clinical responses. In breast cancer (BC) the immunomodulation via chemotherapy (CT) opens possible clinical applications, but: a) the variability in the immune response requires a careful pt selection and b) monitoring immunocompetence in clinical routine still represents a technical challenge.Changes in sub-populations of cytotoxic (CD8+) T-cells (as reported in aging) are not well documented in cancer pts. Methods: We utilized multi-color immunophenotyping by flow cytometry (FCM) using a high-resolution whole-blood assay in 39 pts (median age 53; 34 - 74 yrs) with advanced BC undergoing first-line, standard-dose anthracycline/taxane-based CT and in 12 older healthy women, during a 6-months study, to analyze variations in CD8+ T-cells and the effects of CT on different T-cell sub-populations. Results: In all BC pts there was a consistent decrease in absolute numbers of lymphocytes, T-cells and CD8+ T-cells, starting from the first course and persisting during all the CT program. Among the T-cells, there was a lower CD8-/CD8+ ratio, persisting over 6 months, in pts compared to controls. The proportion of CD28-CD57+ cells also remained higher among pts throughout the sampling duration. The number of CD28+CD57- and CD28-CD5- cells decreased faster during CT than CD28+CD57+ and CD28-CD57+ cells, while only CD28-CD57- cells showed a significant reconstitutive capacity after 6 months.Anti-tumor CT in BC pts can produce clinical benefits also by restoring the responsiveness of T cells and by increasing the frequency and activation of tumor specific T-cells already present in blood before CT. Conclusions: Anthracycline/taxane-based CT is able to elicit changes in the pts immune system. These changes appeared to be pronounced in BC pts, with senescent CD8+ T-cells playing an important role. The pre-treatment condition was not restored after 6 months of CT. Multi-parameter FCM is a powerful tool for detailed analysis of the immune dysfunctions during CT and it will also help the development of combined schedules of CT plus new immunotherapeutic agents.