Control of B-cell lymphoma by therapeutic vaccination and acquisition of immune resistance is independent of direct tumour IFN-gamma signalling

Immunology and Cell Biology
Rory ReardenStephen R Mattarollo

Abstract

Immunomodulatory therapies can effectively control haematological malignancies by promoting antitumour immunity. Previously, we reported transient growth of poorly immunogenic murine non-Hodgkin B-cell lymphomas (B-NHL) by targeting natural killer T (NKT) cells with a therapeutic vaccine approach. Therapeutic efficacy was highly dependent on the ability of the vaccine to provoke rapid interferon-gamma (IFNγ) production from NKT and NK cells. By manipulating the capacity of either host or lymphoma cells to signal through the IFNγ receptor (IFNγR), we investigated whether the therapeutic effect conferred by vaccine-induced IFNγ is a result of immune cell activation, lymphoma IFNγ sensitivity or a combination of both. We demonstrated that antitumour immunity elicited by vaccination requires IFNγ signalling within host cells but not tumour cells. IFNγR-deficient mice failed to mount an effective antitumour immune response following vaccination despite elevated IFNγ levels. With successive exposure to vaccination, lymphomas acquired an increasingly therapy-resistant phenotype and displayed a reduction in major histocompatibility complex I and CD1d surface expression, which is independent of tumour intrinsic IFNγ signalling. Our resu...Continue Reading

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Citations

Apr 24, 2019·Immunology and Cell Biology·Christophe Macri, Justine D Mintern
May 12, 2016·Immunology and Cell Biology·Liza B John, Phillip K Darcy
Oct 6, 2018·Oncoimmunology·Daniel KerageStephen R Mattarollo

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