Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4 + , CD8 + T cells and activate NK cells: a potential candidate molecule for immunotherapy in cervical cancer.

Autor: Dhandapani H; Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Jayakumar H; Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Seetharaman A; Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Singh SS; Department of Pathology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Ganeshrajah S; Department of Radiation Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Jagadish N; Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India., Suri A; Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India., Thangarajan R; Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India., Ramanathan P; Department of Molecular Oncology, Cancer Institute (WIA), Dr. Krishnamurthi Campus, 38, SardarPatel Road, Chennai, 600036, India. priya.serkin@gmail.com.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2021 Sep 07; Vol. 21 (1), pp. 473. Date of Electronic Publication: 2021 Sep 07.
DOI: 10.1186/s12935-021-01951-7
Abstrakt: Background: Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4 + and CD8 + T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4 + and CD8 + T cell responses for future DCs-based vaccine trials in cervical cancer patients.
Methods: Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4 + , CD8 + T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs.
Results: Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3 + Tregs in autologous co-cultures.
Conclusions: In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.
(© 2021. The Author(s).)
Databáze: MEDLINE
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