Immunological alterations in patients with primary tumors in central nervous system

Abstract

-Natural killer (NK) cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS). As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a) determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b) enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c) the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of targetbinding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS. KEY WORDS: brain tumors, NK cells, T cell subsets.Alterações imunológicas em pacientes com tumores primários no sistema nervoso central RESUMO -As células natural killer (NK) desempenham importante papel na vigilância imunológica contra tumores. O objetivo do presente trabalho foi estudar a atividade citotóxica de células NK e as subpopulações de células T no sangue periférico de 13 pacientes com tumores primários no sistema nervoso central (SNC). Como controle foram estudados 29 indivíduos saudáveis com faixa etária equivalente aos pacientes. Os métodos empregados foram: a) determinação da atividade citotóxica de células NK contra células alvo K562; b) quantificação de linfócitos CD3+ e subpopulações CD4+ e CD8+ por meio de anticorpos monoclonais; c) identificação dos tumores por análise histológica e imuno-histoquímica. Os resultados indicaram que adultos e crianças com tumores no SNC apresentam diminuição na percentagem de linfócitos T, da subpopulação de células T auxiliares e da relação células auxiliares/supressoras. A atividade citotóxica de células NK esteve deprimida em pacientes com tumores devido principalmente à diminuição da capacidade de formar conjugados com a célula alvo K562. Os resultados sugerem que a atividade de células NK pode ser afetada por distúrbios imunorregulatórios observados em pacientes com tumores primários no SNC. PALAVRAS-CHAVE: tumores cerebrais, células NK, subpopulações de células T.Most cancers result from interaction of genetic and environment factors; however, genetic factors by themselves explains only about 5% of all cancer. The others have been atributed to environmental factors, that may interact with genetic cancer susceptibility and individual response 1 .

Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members

“…However, the same could not be true for unaffected people. While such study 9 cannot suggest whether the depressed immunity level was secondary to onset of primary brain tumors, or precede it, now this family investigation does indicate that the low immune values can antedate the effect of disease progression and perhaps where involved in the etiological process. NK cell function has been studied in unaffected first-degree relatives of cancer patients in the past 5,6,11 and our results are in agreement with those reports.…”

“…Further investigations to clarify the characteristics of intercellular adhesion molecules may be important, as discussed elsewhere 9 .…”

“…It is difficult, however, to ignore the previous considerations 9 about impairment of cell-mediated and innate immunity induced by cytokines and neurokines shedded by tumors cells and immune system. Recent study explain that low values of T cells in patients with primary brain tumors is due to apoptotic elimination 18 .…”

“…Approximately 2 x 10 5 cells were centrifuged onto a poly-l-lysine-coated coverslip and staining reactions carried out at 4 o . C as described previously 9 . Briefly, after reacting with the monoclonal antibody, the cells were treated with biotinylated horse anti-mouse IgG and fluoresceinated avidin-D and fixed in formaldehyde.…”

“…Our group studied the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS) 9 . The results showed that children and adults with tumors in CNS display altered results of cellular immunity, with reduced percentage of total T cells, helper/inducer subset and low helper/supressor ratio.…”