Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α
1 Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604-1405, USA
2 Research Laboratory of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China
3 Yale University School of Medicine, Department of Internal Medicine, Hematology Section, 333 Cedar Street, P.O. Box 208021, New Haven, Connecticut 06520-8021, USA
BMC Cancer 2010, 10:60 doi:10.1186/1471-2407-10-60Published: 23 February 2010
Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.
CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.
Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4+ T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.
Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.