Efficient killing of radioresistant breast cancer cells by cytokine-induced killer cells

Abstract

Recurrence of breast cancer after radiotherapy may be partly explained by the presence of radioresistant cells. Thus, it would be desirable to develop an effective therapy against radioresistant cells. In this study, we demonstrated the intense antitumor activity of cytokine-induced killer cells against MCF-7 and radioresistant MCF-7 cells, as revealed by cytokine-induced killer–mediated cytotoxicity, tumor cell proliferation, and tumor invasion. Radioresistant MCF-7 cells were more susceptible to cytokine-induced killer cell killing. The stronger cytotoxicity of cytokine-induced killer cells against radioresistant MCF-7 cells was dependent on the expression of major histocompatibility complex class I polypeptide–related sequence A/B on radioresistant MCF-7 cells after exposure of cytokine-induced killer cells to sensitized targets. In addition, we demonstrated that cytokine-induced killer cell treatment sensitized breast cancer cells to chemotherapy via the downregulation of TK1, TYMS, and MDR1. These results indicate that cytokine-induced killer cell treatment in combination with radiotherapy and/or chemotherapy may induce synergistic antitumor activities and represent a novel strategy for breast cancer.

Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma

“…Allogeneic protocols were reported by Iudicone et al [29] and Guo et al [30]. Autologous protocols were also reported by Niam et al [31], Liu et al [32], and Chan and Linn [33], who have obtained CIK cells from patients with myeloid leukemia, hepatocellular carcinoma, and polycythemia, respectively.…”

“…The hypothesis of the protein serum effect on cultured CIK cells was followed by Guo et al [30], Meng et al [21], and Li et al [37]. On the contrary, Niam et al [31] used a complete nutrient medium of RPMI-1640 and 10% fetal calf serum, claiming that this was the optimal medium for CIK cell expansion, better than other serum-free MNCs culture media, despite that, the CD3 + CD56 + effective subset reported comprised a median of 26.6%.…”

“…This finding was supported by Mata-Molanes et al [17], who reported that after 14 days of culture, the percentage of CD3 + CD56 + subset reaches 20 to 30% of the total CIK cells. Guo et al [30], who cultured CIK cells from healthy volunteers' blood donors for 14 days, reported CD3 + CD56 + proportion on day 14 as 25.31 ± 7.42%. Li et al [37], who cultured CIK cells from patients with early-stage melanoma blood for 14 days, reported CD3 + CD56 + proportion on day 14 as 21.8 ± 8%.…”

“…The CIK cells' cytotoxic effect on cancerous cells showed variable degrees of efficacy in several tumors including malignant lymphoma either Hodgkin's disease or non-Hodgkin's lymphoma [49], hematological malignancies as acute myeloid and acute lymphocytic leukemia [50] and chronic lymphocytic leukemia [51]. Recent in vitro studies had further shown the potential activity of CIK cells differentiated from the blood of healthy or patient volunteers against breast cancer [30], pancreatic cancer [52], sarcomas [53], ovarian cancer [44], metastatic melanoma [54], glioblastoma or brain cancer [55], solid tumors [45], and gallbladder cancer [56]. In this study, the cytotoxic effect of CIK cells was investigated on HCC in vitro.…”

<p>¹⁸F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model</p>

“…[6][7][8] Currently, immunotherapy is considered as a promising treatment option for cancer, 9 and adoptive cytokine-induced killer (CIK) cell transfer is commonly used in a variety of tumor immunotherapeutic strategies due to its advantage. [10][11][12][13][14] CIK cells are induced by culturing peripheral blood mononuclear cells (PBMCs) with the addition of an anti-CD3 antibody, recombinant human interleukin (rhIL-1α), recombinant human interferon gamma (rhIFN-γ) and recombinant human interleukin-2 (rhIL-2), and mainly consist of a CD3 + T cell population which simultaneously express a natural killer cell marker CD56. 14 In contrast with other adoptive cell transfer immunotherapies using other subsets of immunologic effector cells, such as tumor-infiltrating lymphocytes, cytotoxic T cells and γδ T cells, [15][16][17] CIK cells tend to proliferate rapidly in vitro and exhibit a strong non-major histocompatibility complex-restricted cytolytic activity.…”