title: Anti-CD20 antibody induces the improvement of cytokine-induced killer cell activity via the STAT and MAPK/ERK signaling pathways.
abstract: There is a current requirement for novel therapeutic strategies for the treatment of hematopoietic tumors. Residual tumor cells are the main origin of tumor relapse. The aim of this study was to eliminate the residual tumor cells of hematopoietic tumors. Cytokine-induced killer (CIK) cells are used in immunotherapy to deplete the residual cells. However, it is necessary to increase the antitumor activity and clinical applicability of CIK cells. The present study investigated the antitumor activity of CIK cells to the SU-DHL2 human B-cell lymphoma and K562 human chronic myelogenous leukemia cell lines. CD3+CD56+cells from healthy donors were expanded in culture with cytokines and anti-CD20 monoclonal antibody (mAb; rituximab) to generate CIK cells. A preliminary investigation of their mechanism was then performed. The increase in the cytotoxicity of the CIK cells induced by the anti-CD20 mAb was associated with an increase in the expression of cytotoxic factors. The expression of components of the signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways was found to increase. Upregulation of the expression of STAT1, STAT3 and STAT5 is important as these co-stimulatory molecules enhance T-cell proliferation. Activation of the MAPK signaling pathway is a possible mechanism for the anti-apoptosis effect on the proliferation of CIK cells. In conclusion, anti-CD20 mAb may play an important role in the improvement of CIK-mediated cytotoxicity to tumor cells. These observations may aid in the improvement of the effects of immunotherapy in depleting the residual cells of hematopoietic tumors. Thus, the use of CIK cells cultured with anti-CD20 mAb could be a novel therapeutic strategy for the depletion of chemotherapy-resistant or residual cells in anaplastic large and B-cell lymphoma.
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Q I
authors.initials: QI
authors.lastname: Deng
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Lv
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
keywords: K562; cell therapy; cytokine-induced killer; human B-cell lymphoma cell lines; rituximab; signaling pathway