Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy

Prajakta Shinde,Vaijayanti Kale,Sameer Melinkeri,Sophia Fernandes,Lalita Limaye

doi:10.1038/s41598-018-23943-w

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.

Highlights

Dendritic cells (DCs) play a pivotal role in the immune system by orchestrating T cell immune response
The mononuclear cell (MNC) population from HD and MM samples were analysed for expression of CD14 to test if there was a difference in the monocyte marker expression
DC cultures were established from adherent monocytes, after seeding equal number of Mono-nuclear cells (MNCs) as described earlier and the viable cells in the adherent fraction were taken

Summary

Introduction

Dendritic cells (DCs) play a pivotal role in the immune system by orchestrating T cell immune response. They capture, process and present antigens to T cells. Multiple myeloma (MM) is a malignancy of plasma cells differentiated from B cells These cells continue to secrete immunoglobulin, which accumulates in the bone marrow and form lesions, hindering normal haematopoiesis. Treatments such as stem cell transplantation (SCT) and chemotherapy have increased the progression-free survival in multiple myeloma patients, they often undergo relapse. Autocrine secretion of IL6 and activation of the P38 MAPK pathway probably contribute to impaired migration of MM-DCs

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