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Exploiting a new strategy to induce immunogenic cell death to improve dendritic cell-based vaccines for lymphoma

B Montico1, C Lapenta2, M Ravo3

  • 1Centro di Riferimento Oncologico, Department of Translational Research, Immunopathology and Cancer biomarkers, Aviano (PN), Italy.

Oncoimmunology
|November 18, 2017
PubMed

Insights

This study developed a novel dendritic cell (DC) vaccine using interferon-conditioned DCs and tumor cell lysates from lymphoma cells. This new approach shows promise for treating aggressive lymphomas by enhancing immune responses and reducing tumor growth.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Development

Background:

  • Dendritic cell (DC)-based vaccines show promise for cancer treatment but face limitations in clinical benefit and optimal antigen formulation.
  • Aggressive and refractory lymphomas require novel therapeutic strategies, including advanced vaccine protocols.

Purpose of the Study:

  • To develop and evaluate a new DC-based vaccination protocol for aggressive lymphomas.
  • To investigate the efficacy of combining interferon-conditioned DCs (IFN-DCs) with tumor cell lysates (TCLs) from lymphoma cells undergoing immunogenic cell death.

Main Methods:

  • Treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) to induce immunogenic cell death.
  • Assessment of DC phagocytosis of RA/IFNα-treated cells and TCLs.
  • Generation of cytotoxic T cells (CTLs) using autologous DCs pulsed with RA/IFNα-TCLs.
  • Evaluation of T-cell responses and tumor growth in NOD/SCID mice reconstituted with human peripheral blood lymphocytes and vaccinated with RA/IFNα-TCL loaded-IFN-DCs.

Main Results:

  • RA/IFNα treatment enhanced the immunogenicity of lymphoma cells, evidenced by increased Calreticulin exposure, CD47 down-regulation, and HMGB1 secretion.
  • DCs efficiently phagocytosed RA/IFNα-treated cells and TCLs.
  • CTLs generated with RA/IFNα-TCL loaded DCs demonstrated specific lysis of lymphoma cells and targets.
  • Vaccination with RA/IFNα-TCL loaded-IFN-DCs in a mouse model led to lymphoma-specific T-cell responses and significant tumor growth reduction.

Conclusions:

  • The combination of RA/IFNα treatment to generate immunogenic TCLs with IFN-DCs represents a feasible and effective strategy for developing anticancer DC-based vaccines.
  • This novel vaccination protocol holds potential for treating aggressive and refractory lymphomas.

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