Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy

Abstract

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p < 0.05) decrease of lymphocyte proliferation and interferon-γ production directly after therapy which lasted until day 28 and was stronger upon stimulation with microbial antigens than with mitogens. Moreover, lymphopenia was revealed, affecting all lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD4+ CD8+ T cells, B cells and NK cells). SIRT led to a reduction in the percentage of activated HLA-DR+ monocytes and of CD45R0+ memory T cells. Higher radiation activity, the presence of liver cirrhosis, chronic kidney disease, diabetes mellitus and metastases were unfavorable factors for immunocompetence, while a better Eastern Cooperative Oncology Group performance status was associated with stronger immunological reactions. In conclusion, SIRT leads to severe impairment of cellular in vitro immune responses. Further studies are needed to assess a potential clinical impact.

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