Cellular Immunity in Breast Cancer Patients Completing Taxane Treatment

Abstract

Purpose: A field study of postchemotherapy immune functioning relative to the use of taxanes is reported. Immune responses in breast cancer patients were analyzed as a function of whether patients received taxane as part of their adjuvant chemotherapy.Experimental Design: Immune levels of 227 stage II/III breast cancer patients were measured immediately after surgery prior to chemotherapy and again 12 months later when all chemotherapies had been completed. T-cell blastogenesis and natural killer (NK) cell lysis levels of patients receiving taxanes (n ‫؍‬ 55) were compared with levels of patients not receiving taxanes (n ‫؍‬ 172).Results: Regression analyses were conducted. The administration of taxane as part of combination chemotherapy predicted increased T-cell blastogenesis and NK cell cytotoxicity after the conclusion of all chemotherapies. For the Taxane group, average phytohemagglutinin-induced blastogenesis was 37% higher and NK cell cytotoxicity was 39% higher than the values for the No-Taxane group.Conclusions: Data from group comparisons with appropriate controls in a sizable clinical sample contravene traditional wisdom that taxanes suppress patients' immune cell functions. Problems in generalizing direct-contact laboratory models to the field of cancer treatment are highlighted.

Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes for Early Breast Cancer According to Disease Subtypes: Sensitivity Analysis of Randomized Trials in Adjuvant and Neoadjuvant Setting

“…Moreover, data suggest that chemotherapy may favor the massive release of tumor associated neo-antigens, which follows cytotoxic-induced cell death (called immunogenic cell death) [41]; may suppress regulatory T cells, thus inhibiting the antitumor response; and may restore cytotoxic T cells [42,43].…”

Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer

“…61), which leads to Th1 activation and production of IFNg that has been implicated in control of cancer growth (62). Evidence also suggests that taxanes could exert an immunostimulatory effect against breast cancer (63)(64)(65)(66) by inducing a Th1 response. Paclitaxel has been shown to stimulate the secretion by macrophages of proinflammatory and Th1 cytokines such as IL1b or IL12 (67,68).…”

“…Paclitaxel has been shown to stimulate the secretion by macrophages of proinflammatory and Th1 cytokines such as IL1b or IL12 (67,68). Carson and colleagues (65) showed that in 227 breast cancer patients, T-cell activation was significantly higher in patients receiving taxanes compared with non-taxane-containing regimens. In contrast, anthracyclines primarily activate CD8 þ T cells rather than CD4 þ T cells to produce IFNg, as shown in mouse models (69).…”

Impaired Natural Killer Cell Lysis in Breast Cancer Patients with High Levels of Psychological Stress is Associated with Altered Expression of Killer Immunoglobin-Like Receptors

“…Dual parameter flow cytometry for CD56 and the above mentioned cell surface markers was employed for characterization of the NK cell population [31]. PBMC were thawed and plated in complete medium at a density of 5 × 10 4 cells/well in 96-well U-bottom plates (Corning Incorporated, Corning, NY) in the presence of IL-2, IL-12, IL-15 (each at 20 ng/well) or control, and incubated for 24 hours (5% CO 2 , 37°C).…”

“…adhesion molecules and KIR's). Dual parameter flow cytometry for CD56 and cell surface markers of NK cell lytic activity was used to characterize the effects of stress on the NK cell phenotype [31]. Cells were examined after 24 hour culture in media or in media supplemented with IL-2, IL-12, or IL-15.…”