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Anti-CD40 predominates over anti-CTLA-4 to provide enhanced antitumor response of DC-CIK cells in renal cell carcinoma

  • Cytokine-induced killer cells (CIK) in combination with dendritic cells (DCs) have shown favorable outcomes in renal cell carcinoma (RCC), yet some patients exhibit recurrence or no response to this therapy. In a broader perspective, enhancing the antitumor response of DC-CIK cells may help to address this issue. Considering this, herein, we investigated the effect of anti-CD40 and anti-CTLA-4 antibodies on the antitumor response of DC-CIK cells against RCC cell lines. Our analysis showed that, a) anti-CD40 antibody (G28.5) increased the CD3+CD56+ effector cells of CIK cells by promoting the maturation and activation of DCs, b) G28.5 also increased CTLA-4 expression in CIK cells via DCs, but the increase could be hindered by the CTLA-4 inhibitor (ipilimumab), c) adding ipilimumab was also able to significantly increase the proportion of CD3+CD56+ cells in DC-CIK cells, d) anti-CD40 antibodies predominated over anti-CTLA-4 antibodies for cytotoxicity, apoptotic effect and IFN-g secretion of DC-CIK cells against RCC cells, e) after ipilimumab treatment, the population of Tregs in CIK cells remained unaffected, but ipilimumab combined with G28.5 significantly reduced the expression of CD28 in CIK cells. Taken together, we suggest that the agonistic anti-CD40 antibody rather than CTLA-4 inhibitor may improve the antitumor response of DC-CIK cells, particularly in RCC. In addition, we pointed towards the yet to be known contribution of CD28 in the crosstalk between anti-CTLA-4 and CIK cells.

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Document Type:Article
Author:Ying Zhang, Xiaolong Wu, Amit Sharma, Hans Weiher, Matthias Schmid, Glen Kristiansen, Ingo G. H. Schmidt-Wolf
Parent Title (English):Frontiers in Immunology
Article Number:925633
Number of pages:14
Publisher:Frontiers Media
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2022/08/25
Copyright:© 2022 Zhang, Wu, Sharma, Weiher, Schmid, Kristiansen and Schmidt-Wolf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Keyword:CD40, CTLA-4; cytokine-induced killer cells; immunotherapy; renal cell carcinoma
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2022/09/08
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International