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Shinde , P. and Fernandes , S. and Melinkeri , S. and Kale , V. and Limaye , L. (2018) Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy. Scientific Report. 5705 .

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65.Dr. Kale (Sci. Rep.) open access.pdf

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Abstract

Dendritic cells (DCs) have the potential to elicit long-lasting anti-tumour immune responses. Most of the clinical trials of anti-cancer DC vaccines are based on monocyte-derived DCs (Mo-DCs). However, their outcomes have shown limited promise especially in multiple myeloma (MM) patients. Here, we investigated whether in vitro generated Mo-DCs from MM patients (MM-DCs) possess impaired functionality, thus contributing to the limited success of DC vaccines. We generated MM-DCs and compared them with DCs from healthy donors (HD-DCs). The yield of DCs in MM was 3.5 fold lower than in HD sets. However morphology, phenotype, antigen uptake and allo-T cell stimulation were comparable. Migration and secretion of IL12p70 and IFN-γ (in DC-T cell co-cultures) were significantly reduced in MM-DCs. Thus, MM-DCs were compromised in functionality. This impairment could be attributed to autocrine secretion of IL6 by MM-monocytes and activation of their P38 MAPK pathway. This indicates a need to look for alternative sources of DCs.

Item Type: Article
Subjects: Cancer Biology
Depositing User: Mr. Rameshwar Nema
Date Deposited: 17 Dec 2018 05:48
Last Modified: 19 Feb 2021 06:41
URI: http://nccs.sciencecentral.in/id/eprint/559

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