Cytokine-induced killer cells (CIK cells) are a heterogeneous population of cells generated from peripheral blood mononuclear cells, which share phenotypic and functional properties with both natural killer and T cells. CIK cells
therapy, as an adoptive immunotherapy with strong antitumor activity in vitro, represents a promising approach for the treatment of a broad array of malignant
tumors. However, clinical trials in CIK cells
therapy did not show more noticeable improvement as anticipated in cure rates or long-term survival. Possible explanations are that abnormal
tumor vasculature and hypoxic microenvironment may highly limit the therapeutic benefits of CIK cells
therapy. We hypothesized that antiangiogenesis
therapy could enhance the antitumor efficacy of CIK cells by normalizing
tumor vasculature and modulating
tumor hypoxic microenvironment. In this study, we combined
bevacizumab and adoptive CIK cells
therapy in the treatment of
lung adenocarcinoma bearing murine models. Flow cytometry, intravital microscopy and immunohistochemistry were applied to detect
tumor vasculature and hypoxic microenvironment as well as the infiltration of CIK cells. The results indicated that
bevacizumab-combined adoptive CIK cells had synergistic inhibition effects on the growth of
lung adenocarcinoma.
Hypoxia significantly inhibited the infiltration of CIK cells into
tumor tissue.
Bevacizumab could normalize
tumor vasculature and decrease
tumor hypoxic area. Furthermore, combination
therapy enhanced more CIK cells infiltrated into
tumor compared with other treatment.
Bevacizumab improves antitumor efficacy of CIK cells transfer
therapy in
non-small cell lung cancer (NSCLC). The study provides a reasonable and beneficial strategy that combined antiangiogenesis
therapy with CIK cells
therapy for patients of advanced stage
non-small cell lung cancer.