Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil,epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study |
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Authors: | Fariba Mozaffari Christina Lindemalm Aniruddha Choudhury Helena Granstam-Björneklett Mats Lekander Bo Nilsson Marja-Leena Ojutkangas Anders Österborg Leif Bergkvist Håkan Mellstedt |
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Institution: | Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska University Hospital Solna, Stockholm, Sweden. |
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Abstract: | Immunotherapy is being increasingly utilized for adjuvant treatment for breast cancer (BC). We have previously described immune
functions during primary therapy for BC. The present study describes immune recovery patterns during long-term, unmaintained
follow-up after completion of adjuvant therapy.A group of patients with primary BC had been treated with adjuvant radio-chemotherapy
(RT + CT) 5-fluorouracil, epirubicin and cyclophosphamide (FEC) (n = 21) and another group with radiotherapy (RT) (n = 20) alone. Immunological testing of NK and T-cell functions was performed initially at the end of adjuvant treatment and
repeated after 2, 6 and 12 months. NK cell cytotoxicity was significantly higher (P < 0.05) at all time-points in patients than in age-matched controls and did not differ between the two treatments groups
during one year observation. In contrast, lower numbers of CD4 T-cells and lower expression of CD28 on T-cells was observed
particularly in RT + CT patients and did not normalize during the observation period. The numbers of Treg cells (CD4+CD25high) were low in the RT + CT group during follow-up, as well as expression of TCRξ, Zap70, p56lck, P59fyn and PI3 k in CD4+ cells. In contrast, expression of intracellular cytokines (IFN-γ, IL-2, IL-4) in CD4 and CD8 T cells were significantly higher
in RT + CT patients than in the RT group and the difference increased during follow-up. In conclusion, NK-cell cytotoxicity
increased during unmaintained long-term follow-up whereas CD4 and regulatory T cells as well as signal transduction molecules
remained low following adjuvant radio-chemotherapy. |
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Keywords: | Breast cancer NK cells T cells Radiation Chemotherapy |
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