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Mol Med. 2017 Oct;23:235-246. doi: 10.2119/molmed.2017.00084. Epub 2017 Aug 9.

Analytic and Dynamic Secretory Profile of Patient-Derived Cytokine-Induced Killer Cells.

Author information

1
Division of Medical Oncology, Experimental Cell Therapy, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.
2
Centre for Regenerative Medicine "Stefano Ferrari," Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
3
Department of Life Science and Biotechnology, Sections of Microbiology and Applied Pathology; Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
4
Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Torino, Torino, Italy.
5
Department of Oncology, University of Torino, Candiolo, Torino, Italy.

Abstract

Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion. Mature CIK cells (day 21) produce a great variety of interleukins and secreted proteins that can be divided into 3 groups based on their secretion quantity: high (IL-13, RANTES, MIP-1α and 1β), medium (IL-1Ra, IL-5, IL-8, IL-10, IL-17, IP-10, INF-γ, VEGF and GMCSF) and low (IL-1β, IL-4, IL-6, IL-7, IL-9, IL-12, IL-15, Eotaxin, PDGF-bb, FGF basic, G-CSF and MCP-1) secreted. Moreover, comparing PBMC (day 1) and mature CIK cells (day 14 and 21) secretome, we observed that IL-5, IL-10, IL-13, GM-CSF, VEGF resulted greatly up-regulated, while IL-1β, IL-6, IL-8, IL-15, IL-17, eotaxin, MCP-1, and RANTES were down-regulated. We also performed a gene expression profile analysis of patient-derived CIK cells showing that mRNA for the different cytokines and secreted proteins were modulated during PBMC to CIK differentiation. We highlighted previously unknown secretory properties and provided for the first time a comprehensive molecular characterization of CIK cells. Our findings provide rationale to explore the functional implications and possible therapeutic modulation of CIK secretome.

KEYWORDS:

CIK cells; Cancer; Cytokines; Secretome; Transcriptome

PMID:
28805233
PMCID:
PMC5630476
DOI:
10.2119/molmed.2017.00084
[Indexed for MEDLINE]
Free PMC Article

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