Factors of local immunity in patients with rectal cancer after prolonged radiotherapy.

Abstract

e15164 Background: Immunological study of the blood and tumor tissues was performed in patients with rectal cancer receiving neoadjuvant chemoradiotherapy. Methods: 30 patients with rectal cancer (13 women and 17 men aged 37-68 years with stage II-III adenocarcinomas G1-G3) were divided into groups according to results of DNA cytometry and their response to neoadjuvant treatment. When tumor proliferative activity was stable for 4 weeks of treatment, patients received surgery on time (group 1), while patients with verified inhibition of tumor proliferation (the index decrease by 1.5 times and more) continued treatment for 6-8 weeks and then were operated on (group 2). The immune status of patients (T, B, NK, DN, Tregs) was assessed during treatment. Homogenates of tumor tissue samples obtained during surgery were studied for the levels of lymphocytes (flow cytometry) and cytokines TNF-α, IL-1ß, IL-1RA, IL-6, IL-8, IFN-α, IFN-γ (ELISA); tumor proliferation index was assessed by DNA cytometry. Results were analyzed by Statistica 10.0 program. Results: The dynamics of parameters of the cellular immunity was different in patients of two groups. In group 1, percentage of T lymphocytes in blood decreased (from 66.7±3.3 to 50.4±1.6%), as well as their main subsets (CD4+ and CD8+ cells: from 33.6±2.7 to 27.0±1.7% and from 26.7±2.4 to 20.7±1.7% respectively). Patients of group 2 developed an increase in levels of NK cells from 10.1±1.2 to 15.3±2.2%, and levels of CD3+, CD4+ and CD8+ cells were significantly higher than in group 1: 35.0±1.8% for CD4+ and 28.3±2.9% for CD8+ (p < 0.05). The groups also differed in indices of local immunity: DN cells levels in group 2 were lower than in group 1 (5.8±1.0 vs. 18.4±5.4%) and CD4+ were higher (36.6±3.3 vs. 26.2±3.1%; p < 0.05). Patients of group 2 showed lower levels of IL-1ß, IL-6, IL-10, while IFNγ was elevated by 5.4 times, indicating a more favorable local cytokine status of the patients, compared to group 1. Conclusions: In rectal cancer patients with effect confirmed by DNA cytometry, prolongation of chemoradiotherapy to 6-8 weeks provides the formation of a more favorable immunological microenvironment of the tumor, and in such cases it is considered appropriate.