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Induction of antigen-specific effector-phase tolerance following vaccination against a previously ignored B-cell lymphoma


Prato, S; Mintern, JD; Lahoud, MH; Huang, DC; Villadangos, JA
2011-07
IMMUNOLOGY AND CELL BIOLOGY
Journal Article
89
5
595-603
The mechanisms of immune evasion during haematological malignancies are poorly understood. As lymphomas grow in lymphoid organs, it would be expected that if these lymphomas express neo-antigens they should be readily detected by the immune system. To test this assumption, we generated a new non-Hodgkin B-cell lymphoma model expressing the model tumour neo-antigen Ovalbumin (OVA), and analysed the endogenous antigen-specific CD8(+) T-cell response that it elicited in recipient mice. The OVA+ lymphoma cells were eliminated by cytotoxic T lymphocytes (CTL) in mice that had been previously vaccinated against OVA. In contrast, the immune system of naive mice ignored the malignant cells even though these continuously expressed and presented OVA on their MHC class I molecules. This state of ignorance could be overcome by therapeutic vaccination, which led to the expansion of endogenous anti-OVA-specific CD8(+) T cells. However, the cytotoxic and interferon-gamma secretion capacity of these T cells were impaired. The tumour model that we describe thus reproduces several key aspects of human lymphoma; tumor ignorance can be broken by vaccination but the ensuing immune response remains ineffective. This model can be exploited to further understand the mechanisms of lymphoma immunoevasion and devise effective immunotherapy. Immunology and Cell Biology (2011) 89, 595-603; doi:10.1038/icb.2010.131; published online 16 November 2010
NATURE PUBLISHING GROUP
CYTOTOXIC T-LYMPHOCYTES; ACUTE LYMPHOBLASTIC-LEUKEMIA; CROSS-PRESENTATION; CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; TUMOR PROGRESSION; EXPRESSED ANTIGEN; DENDRITIC CELLS; IN-VIVO; MECHANISM
Immunology
10.1038/icb.2010.131
© 2013 Australasian Society for Immunology

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Creation Date 2011-07-01 12:00:00