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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 708-716

Tumor suppressive effects of WEE1 gene silencing could not enhance immunopotentiation effects of CD80 and 4-1BBL co-stimulation in human T cells


1 School of Medicine, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran; Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
2 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3 Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
4 School of Medicine, Shiraz Institute for Cancer Research; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5 UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor DE, Malaysia
6 School of Medicine, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
7 Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Correspondence Address:
Mansooreh Jaberipour
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.147746

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Background: Activation of T cells against tumors by recruiting co-stimulatory molecules has been an attractive approach for cancer immunotherapy. Reports suggested that targeting different genes in tumors might also boost T cell-mediated tumor destruction. Aims: We investigated whether in vitro WEE1 gene silencing in MDA-MB-468 and MCF7 breast cancer cell lines could enhance immunopotentiating effects of CD80 and 4-1BBL co-stimulation in human T cells. Materials and Methods: WEE1 gene was specifically silenced in the cancer cells using shRNA technology. The co-stimulatory molecules were over-expressed on the surface of the cancer cells by recombinant non-replicative adenoviruses. The immune reaction of T cells in the co-culture with tumor cells was studied. IFN-g production was assessed by intracellular staining of T cells. To assess cytotoxic activity of CD8 + T cells, the CD107a mobilization-degranulation assay was performed. Expression of granzyme B, perforin and fasl were examined by real time PCR. Results: T cell dual co-stimulation led to a significant increase in the frequency of IFN-g producing cells and higher percentages of degranulation in CD8 + T cells. It also resulted in higher expression levels of the cytotoxicity-related genes. WEE1 gene silencing in the target cells alone however, could not produce significant immune reactivation in the cultured T cells. Likewise, the immune responses of T cells neither improved nor suppressed when dually co-stimulated PBMCs were exposed to the cancer cells with silenced WEE1. Conclusions: In spite of antitumor effects of WEE1 silencing, combination of this approach with immune co-stimulation could not boost the reactivity of cultured T cells against the tested breast cancer cells.


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