Format

Send to

Choose Destination
J Immunol. 2016 Aug 1;197(3):795-806. doi: 10.4049/jimmunol.1600262. Epub 2016 Jun 29.

NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients.

Author information

1
Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy;
2
Unità di Chirurgia Generale, Azienda Ospedaliera Sant'Andrea, Università La Sapienza, 00189 Rome, Italy; and.
3
Unità di Ematologia, Azienda Ospedaliera Sant'Andrea, Università La Sapienza, 00189 Rome, Italy.
4
Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy; stefano.santini@iss.it.

Abstract

Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte-derived dendritic cells generated in the presence of IFN-α and GM-CSF (IFN-DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell-loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-γ production and a remarkable increase in CD8(+) and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-γ production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I-related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IFN-γ production. The overall results indicate that IFN-DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8(+) T cell antitumor immunity.

PMID:
27357153
DOI:
10.4049/jimmunol.1600262
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center