Simultaneous detection of circulating immunological parameters and tumor biomarkers in early stage breast cancer patients during adjuvant chemotherapy

被引:8
作者
Rovati, B. [1 ,2 ]
Mariucci, S. [1 ,2 ]
Delfanti, S. [1 ,2 ]
Grasso, D. [1 ,2 ]
Tinelli, C. [3 ]
Torre, C. [4 ]
De Amici, M. [4 ]
Pedrazzoli, P. [1 ,2 ]
机构
[1] Fdn IRCCS Policlin San Matteo, SC Oncol, Pavia, Italy
[2] Fdn IRCCS Policlin San Matteo, Lab Citofluorimetria & Terapie Cellulari, Pavia, Italy
[3] Fdn IRCCS Policlin San Matteo, Serv Biometria & Stat Med, Pavia, Italy
[4] Fdn IRCCS Policlin San Matteo, Lab Immuno Allergol, SC Pediat, Pavia, Italy
关键词
Adjuvant breast cancer chemotherapy; Cytokine; Lymphocyte subsets; Dendritic cells; Endothelial cells; Tumor cells; ENDOTHELIAL PROGENITOR CELLS; HER2 EXTRACELLULAR DOMAIN; BLOOD LEUKOCYTE PHENOTYPE; FLOW-CYTOMETRIC METHOD; PERIPHERAL-BLOOD; DENDRITIC CELLS; LYMPHOCYTE SUBSETS; GROWTH-FACTOR; T-CELLS; ANTINEOPLASTIC THERAPY;
D O I
10.1007/s13402-015-0264-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. 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. 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. 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.
引用
收藏
页码:211 / 228
页数:18
相关论文
共 85 条
[1]   A Common and Functional Gene Variant in the Vascular Endothelial Growth Factor A Predicts Clinical Outcome in Early-Stage Breast Cancer [J].
Absenger, Gudrun ;
Szkandera, Joanna ;
Stotz, Michael ;
Pichler, Martin ;
Winder, Thomas ;
Langsenlehner, Tanja ;
Langsenlehner, Uwe ;
Samonigg, Hellmut ;
Renner, Wilfried ;
Gerger, Armin .
MOLECULAR CARCINOGENESIS, 2013, 52 :96-102
[2]  
Almand B, 2000, CLIN CANCER RES, V6, P1755
[3]   World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects [J].
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2013, 310 (20) :2191-2194
[4]   Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients [J].
Beerepoot, LV ;
Mehra, N ;
Vermaat, JSP ;
Zonnenberg, BA ;
Gebbink, MFGB ;
Voest, EE .
ANNALS OF ONCOLOGY, 2004, 15 (01) :139-145
[5]   CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer [J].
Borg, C ;
Ray-Coquard, I ;
Philip, I ;
Clapisson, G ;
Bendriss-Verma, N ;
Menetrier-Caux, C ;
Sebban, C ;
Biron, P ;
Blay, JY .
CANCER, 2004, 101 (11) :2675-2680
[6]   Immune dysfunction and micrometastases in women with breast cancer [J].
Campbell, MJ ;
Scott, J ;
Maecker, HT ;
Park, JW ;
Esserman, LJ .
BREAST CANCER RESEARCH AND TREATMENT, 2005, 91 (02) :163-171
[7]  
Campoli M, 2005, CANC TREAT, V123, P61
[8]   Evidence for immune defects in breast and lung cancer patients [J].
Caras, I ;
Grigorescu, A ;
Stavaru, C ;
Radu, DL ;
Mogos, I ;
Szegli, G ;
Salageanu, A .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2004, 53 (12) :1146-1152
[9]   The immunological effects of taxanes [J].
Chan, OTM ;
Yang, LX .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2000, 49 (4-5) :181-185
[10]   Effect of peg-filgrastim-supported dose-dense adjuvant chemotherapy on the peripheral blood leukocyte phenotype in breast cancer patients [J].
Collova, Elena ;
Rovati, Bianca ;
Grasso, Donatella ;
Bencardino, Katia ;
Manzoni, Mariangela ;
Danova, Marco .
MOLECULAR MEDICINE REPORTS, 2009, 2 (01) :85-88