Naive Tumour‐Specific CD4+ T Cells were Efficiently Primed in Acute Lymphoblastic Leukaemia

The recognition and neutralization of tumour cells is one of the big challenges in immunity. The immune system has to recognize syngeneic tumour cells and has to be primed and respond in an adequate manner. Priming of a leukaemia‐specific immune response is a crucial step in tumour immunology that c...

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Published in:	Scandinavian journal of immunology Vol. 80; no. 3; pp. 161 - 168
Main Authors:	Noyan, F., Lieke, T., Taubert, R., Sievers, M., Dywicki, J., Hapke, M., Falk, C. S., Manns, M. P., Jaeckel, E., Hardtke‐Wolenski, M.
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-09-2014
Subjects:	Animals Bone Marrow Cells - immunology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - transplantation Cell Line, Tumor Cells, Cultured Dendritic Cells - immunology Female Flow Cytometry Green Fluorescent Proteins - genetics Green Fluorescent Proteins - immunology Immunotherapy, Adoptive - methods Interferon-gamma - blood Interferon-gamma - immunology Interferon-gamma - metabolism Interleukin-10 - blood Interleukin-10 - immunology Interleukin-10 - metabolism Interleukin-12 - blood Interleukin-12 - immunology Interleukin-12 - metabolism Interleukin-2 - blood Interleukin-2 - immunology Interleukin-2 - metabolism Kaplan-Meier Estimate Lymphocyte Activation - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, SCID Ovalbumin - genetics Ovalbumin - immunology Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy Time Factors
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Summary:	The recognition and neutralization of tumour cells is one of the big challenges in immunity. The immune system has to recognize syngeneic tumour cells and has to be primed and respond in an adequate manner. Priming of a leukaemia‐specific immune response is a crucial step in tumour immunology that can mislead to tumour tolerance either by T cell ignorance, deletion or Treg induction. To resemble the situation of acute lymphoblastic leukaemia (ALL) in patients, we used the murine BALB/c model with syngeneic BM185 tumour cells. We established a tumour cell line that expresses the neo‐antigen ovalbumin (BM185‐OVA/GFP) to allow the application of T cell receptor transgenic, antigen‐specific CD4+ T cells. Here, we demonstrate that effective anti‐ALL immunity can be established by in vivo priming of CD4+ T cells that is sufficient to differentiate into effector cells. Yet they failed to control tumour alone, but initiated a Th1 response. An efficient tumour clearance was dependent on both antigen‐specific CD4+ T cells and CD8+ effector T cells from the endogenous repertoire. The tolerogeneic milieu was characterized by increased Tregs numbers and elevated IL‐10 level. Tregs hamper effective antitumour immune response, but their depletion did not result in reduced tumour growth. In contrast, neutralization of IL‐10 improved median mouse survival. Future therapies should focus on establishing a strong CD4+ T cells response, either by adjuvant or by adoptive transfer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0300-9475 1365-3083
DOI:	10.1111/sji.12198