Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

Department of Pathology and Department of Medicine, Section of Hematology/Oncology, the University of Chicago, Chicago, IL, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 09/2011; 208(10):2005-16. DOI: 10.1084/jem.20101159
Source: PubMed

ABSTRACT Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c(+) cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α(+) dendritic cells, which were demonstrated to be essential using Batf3(-/-) mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α(+) DCs.

Download full-text


Available from: Seng-Ryong Woo, Jul 29, 2015
  • Source
    • "Over the past few decades, the GC prognosis continues to be poor, with 5-year survival rates of approximately 20% [1] [4]. The reasons for metastasis and recurrence of GC can be summarized as following: (I) The intrinsic antigenicity weakness of tumor cells [5] [6], immunological surveillance of the host can not identify and eliminate the malignant cells that distributed out of the resection field and the peripheral lymphoid organs. (II) Immunological surveillance defect or dysfunction of the host. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cells (DCs) have displayed the promising potential in cancer immunity. How to enhance DCs immunotherapeutic effect in cancer targeted immunotherapy and prevention is still a great challenge. Herein, we report for the first time the allogenic DCs and tumor cell fused vaccine combined with cytokine induced killing cells (CIKs) for targeted imaging and enhanced immunotherapeutic efficacy of gastric cancer (GC). The fused vaccine was prepared by PEG mediated fusion between mature DCs and inactive gastric cancer MGC803 cells. The immunotherapeutic and prophylactic potential of the fused cells (FCs) were evaluated in tumor-bearing, post-surgery and tumor free mice models. The migration and homing process of near infrared region quantum dots (NIR-QDs) labeled FCs were investigated by real-time animal imaging system. Results showed that the FCs and FC + CIKs could trigger the tumor-specific CTLs against GC cells, target the tumor tissue initiatively and enhance the prophylactic effects, suppress the tumor growth remarkably in vivo. The potential mechanism is also investigated. In conclusion, allogenic DCs and tumor cell fused vaccine can be used for targeted imaging and enhanced immunotherapeutic efficacy of GC, and the FC + CIKs strategy own great potential in clinical applications such as early therapy and prevention of tumor-metastasis and relapse in near future. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 54. DOI:10.1016/j.biomaterials.2015.03.024 · 8.31 Impact Factor
  • Source
    • "They can internalize tumor antigen and cross-present it to T-cells within the draining lymph node. This is an important step towards an antitumoral immune reaction [117]. However, controversial data exists on their role in the tumor microenvironment, DC activation, or tolerance induction. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphangiogenesis is a very early step in lymphatic metastasis. It is regulated and promoted not only by the tumor cells themselves, but also by cells of the tumor microenvironment, including cancer associated fibroblasts, mesenchymal stem cells, dendritic cells, or macrophages. Even the extracellular matrix as well as cytokines and growth factors are involved in the process of lymphangiogenesis and metastasis. The cellular and noncellular components influence each other and can be influenced by the tumor cells. The knowledge about mechanisms behind lymphangiogenesis in the tumor microenvironmental crosstalk is growing and offers starting points for new therapeutic approaches.
    BioMed Research International 09/2014; 2014:639058. DOI:10.1155/2014/639058 · 2.71 Impact Factor
  • Source
    • "For example, we have found that some regressors are well recognized by NK cells whereas others are not, and this is not always correlated with NKG2D ligand expression (O'Sullivan et al., 2011), even though NK cells and NKG2D are important for tumor surveillance (Guerra et al., 2008; Smyth et al., 2005). Furthermore, some regressors require type I interferon for their rejection whereas others do not (Dunn et al., 2005), even though IFNAR À/À mice lacking interferon a/b (IFNa/b) responsiveness are more susceptible to cancer (Diamond et al., 2011; Dunn et al., 2005; Fuertes et al., 2011), and IFNa/b is used in the treatment of melanoma (Garbe et al., 2011). We therefore conclude that IL-17D is one of many genes that regressor cells produce that can stimulate antitumor immunity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The process of cancer immunoediting generates a repertoire of cancer cells that can persist in immune-competent hosts. In its most complex form, this process begins with the elimination of highly immunogenic unedited tumor cells followed by the escape of less immunogenic edited cells. Although edited tumors can release immunosuppressive factors, it is unknown whether unedited tumors produce cytokines that enhance antitumor function. Utilizing gene microarray analysis, we found the cytokine interleukin 17D (IL-17D) was highly expressed in certain unedited tumors but not in edited mouse tumor cell lines. Moreover, forced expression of IL-17D in edited tumor cells induced rejection by stimulating MCP-1 production from tumor endothelial cells, leading to the recruitment of natural killer (NK) cells. NK cells promoted M1 macrophage development and adaptive immune responses. IL-17D expression was also decreased in certain high-grade and metastatic human tumors, suggesting that it can be targeted for tumor immune therapy.
    Cell Reports 04/2014; 7(4). DOI:10.1016/j.celrep.2014.03.073 · 7.21 Impact Factor
Show more