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  • Title: Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma.
    Author: Fattorossi A, Battaglia A, Ferrandina G, Coronetta F, Legge F, Salutari V, Scambia G.
    Journal: Cancer; 2004 Apr 01; 100(7):1418-28. PubMed ID: 15042676.
    Abstract:
    BACKGROUND: The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma. METHODS: Uninvolved tumor-draining lymph nodes (TDLN) (n=158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)-treated patients, and 19 chemoradiation (CR)-treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon-gamma (IFN-gamma) production. Lymphocyte subsets in peripheral blood also were assessed. RESULTS: TDLNs from CR-treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT-treated patients (P values ranged from <0.05 to <0.01). TDLNs from CR-treated patients were enriched in activated-type CD4+ cells (HLA-DR+, CD134+, CD62L-, and CD25+ at an intermediate expression level; P values ranged from <0.05 to <0.01) and activated-type CD8+ cells (CD62L-, P<0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of naïve-type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P<0.01 and <0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN-gamma. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy-induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood. CONCLUSIONS: To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma.
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