Immunosuppressive Strategies that are Mediated by Tumor Cells

Division of Immunogenetics, Hospital de Clínicas José de San Martín, University of Buenos Aires, Buenos Aires, Argentina.
Annual Review of Immunology (Impact Factor: 39.33). 02/2007; 25(1):267-96. DOI: 10.1146/annurev.immunol.25.022106.141609
Source: PubMed


Despite major advances in understanding the mechanisms leading to tumor immunity, a number of obstacles hinder the successful translation of mechanistic insights into effective tumor immunotherapy. Such obstacles include the ability of tumors to foster a tolerant microenvironment and the activation of a plethora of immunosuppressive mechanisms, which may act in concert to counteract effective immune responses. Here we discuss different strategies employed by tumors to thwart immune responses, including tumor-induced impairment of antigen presentation, the activation of negative costimulatory signals, and the elaboration of immunosuppressive factors. In addition, we underscore the influence of regulatory cell populations that may contribute to this immunosuppressive network; these include regulatory T cells, natural killer T cells, and distinct subsets of immature and mature dendritic cells. The current wealth of preclinical information promises a future scenario in which the synchronized blockade of immunosuppressive mechanisms may be effective in combination with other conventional strategies to overcome immunological tolerance and promote tumor regression.

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Available from: Eduardo M Sotomayor, Feb 21, 2014
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    • "Passive and active immunotherapy has been successfully applied to the treatment of a wide variety of human cancers [8] and holds promise of a lifelong cure [9]. However, tumor-induced immunosuppression still represents a major obstacle to effective cell-mediated immunity and immunotherapy [3] [5]. Accordingly, more insights into the main mechanisms associated with immune responses based on tumor specific features are required to obtain successful therapeutic outcomes with immunomodulatory strategies. "
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    Virulence 07/2015; DOI:10.1080/21505594.2015.1076614 · 4.22 Impact Factor
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    • "In addition , several mechanisms may inhibit the function of adoptively transferred CAR T cells. These mechanisms include suppressor cells such as Tregs cells, myeloid-derived suppressor cells (MDSCs), and immunosuppressive molecules/ cytokines (e.g., TGF-b) (Rabinovich et al. 2007, Schreiber et al. 2011). Moreover, some genetic modifications mentioned above can also help genetically modified T cells to resist immunosuppressive factors in the tumor microenvironment . "
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    • "Peripheral immune tolerance is important to prevent autoimmune disorders. However, tumor cells use immune checkpoints to prevent immune recognition (Zitvogel et al, 2006; Rabinovich et al, 2007). Blocking antibodies against surface-expressed immune-regulatory proteins, such as CTLA4 and PD-L1 (Chambers et al, 2001; Blank et al, 2004), boost anti-tumor immunity and are successfully applied in clinical trials (van Elsas et al, 1999; Weber, 2007; Brahmer et al, 2012; Topalian et al, 2012). "
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