Cancer induces tolerance by suppressing immune function, modulating the T helper activity and causing an imbalance of cytokines produced by T cells. IL-12 is an immune regulatory cytokine with potent anti-tumor activity and its signalling network leads to polarization of na?ve CD4+ T cells into Th1. In pre-clinical studies, administration of recombinant IL-12 by intravenous injection or IL-12 plasmid DNA by intra-tumoral injection showed some anti-tumor effects, measurable immunological responses, but also important dose-dependent side effects. We investigated the ability of low doses of IL-12 to modulate the T cell subpopulations in cultures of PBMCs derived from Non Small Lung Cancer (NSCLC) patients and to induce lysis of lung adenocarcinoma cells by T cells. PBMCs were stimulated with different doses of IL-12 and T cell phenotype was evaluated. IL-12 at 0.01 pg/ml significantly increased the number of CD4 and CD8 T cells, in particular of CD4/IFNγ producing cells. IL-12 did not stimulate T regulatory, but it increased the lysis of lung adenocarcinoma cells induced by T cells. Our results showed that low doses of IL-12 modulates T cell sub-populations in vitro and it increased their lytic activity on adenocarcinoma cells, thus we hypothesize the use of low dose of IL-12 as a therapeutic tool against pathologies characterized by a T cell imbalance, in order to promote an immuno-modulation.
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D’Amico et al. (2012) studied this question.
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