B Rovati1, S Mariucci2, S Delfanti2, D Grasso2, C Tinelli3, C Torre4, M De Amici4, P Pedrazzoli2. 1. SC Oncologia e Laboratorio di Citofluorimetria, e Terapie Cellulari, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. b.rovati@smatteo.pv.it. 2. SC Oncologia e Laboratorio di Citofluorimetria, e Terapie Cellulari, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 3. Servizio di Biometria e Statistica Medica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 4. SC Pediatria, Laboratorio di Immuno Allergologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Abstract
BACKGROUND: Chemotherapy-induced immune suppression has mainly been studied in patients with advanced cancer, but the influence of chemotherapy on the immune system in early stage cancer patients has so far not been studied systematically. The aim of the present study was to monitor the immune system during anthracycline- and taxane-based adjuvant chemotherapy in early stage breast cancer patients, to assess the impact of circulating tumor cells on selected immune parameters and to reveal putative angiogenic effects of circulating endothelial cells. METHODS: Peripheral blood samples from 20 early stage breast cancer patients were analyzed using a flow cytometric multi-color of antibodies to enumerate lymphocyte and dendritic cell subsets, as well as endothelial and tumor cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of various serological factors. RESULTS: During chemotherapy, all immunological parameters and angiogenesis surrogate biomarkers showed significant decreases. The numbers of circulating tumor cells showed significant inverse correlations with the numbers of T helper cells, a lymphocyte subset directly related to effective anti-tumor responses. Reduced T helper cell numbers may contribute to systemic immunosuppression and, as such, the activation of dormant tumor cells. CONCLUSIONS: From our results we conclude that adjuvant chemotherapy suppresses immune function in early stage breast cancer patients. In addition, we conclude that the presence of circulating tumor cells, defined as pan-cytokeratin(+), CD326(+), CD45(-) cells, may serve as an important indicator of a patient's immune status. Further investigations are needed to firmly define circulating tumor cells as a predictor for the success of breast cancer adjuvant chemotherapy.
BACKGROUND: Chemotherapy-induced immune suppression has mainly been studied in patients with advanced cancer, but the influence of chemotherapy on the immune system in early stage cancerpatients has so far not been studied systematically. The aim of the present study was to monitor the immune system during anthracycline- and taxane-based adjuvant chemotherapy in early stage breast cancerpatients, to assess the impact of circulating tumor cells on selected immune parameters and to reveal putative angiogenic effects of circulating endothelial cells. METHODS: Peripheral blood samples from 20 early stage breast cancerpatients were analyzed using a flow cytometric multi-color of antibodies to enumerate lymphocyte and dendritic cell subsets, as well as endothelial and tumor cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of various serological factors. RESULTS: During chemotherapy, all immunological parameters and angiogenesis surrogate biomarkers showed significant decreases. The numbers of circulating tumor cells showed significant inverse correlations with the numbers of T helper cells, a lymphocyte subset directly related to effective anti-tumor responses. Reduced T helper cell numbers may contribute to systemic immunosuppression and, as such, the activation of dormant tumor cells. CONCLUSIONS: From our results we conclude that adjuvant chemotherapy suppresses immune function in early stage breast cancerpatients. In addition, we conclude that the presence of circulating tumor cells, defined as pan-cytokeratin(+), CD326(+), CD45(-) cells, may serve as an important indicator of a patient's immune status. Further investigations are needed to firmly define circulating tumor cells as a predictor for the success of breast cancer adjuvant chemotherapy.
Entities:
Keywords:
Adjuvant breast cancer chemotherapy; Cytokine; Dendritic cells; Endothelial cells; Lymphocyte subsets; Tumor cells
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