%A Ondondo,Beatrice %D 2014 %J Frontiers in Immunology %C %F %G English %K regulatory T cells,Immune-dysfunction,immune-regulation,IBD,Cancer,HIV-1 %Q %R 10.3389/fimmu.2014.00090 %W %L %M %P %7 %8 2014-March-06 %9 Review %+ Dr Beatrice Ondondo,PhD,Oxford University,The Jenner Institute, Nuffield Department of Medicine,ORCRB,Roosevelt Drive,Oxford,OX3 7DQ,United Kingdom,beatriceo32@gmail.com %# %! Intricate complexities of immune-regulation and cancer %* %< %T Fallen Angels or Risen Apes? A Tale of the Intricate Complexities of Imbalanced Immune Responses in the Pathogenesis and Progression of Immune-Mediated and Viral Cancers %U https://www.frontiersin.org/articles/10.3389/fimmu.2014.00090 %V 5 %0 JOURNAL ARTICLE %@ 1664-3224 %X Excessive immune responses directed against foreign pathogens, self-antigens, or commensal microflora can cause cancer establishment and progression if the execution of tight immuno-regulatory mechanisms fails. On the other hand, induction of potent tumor antigen-specific immune responses together with stimulation of the innate immune system is a pre-requisite for effective anti-tumor immunity, and if suppressed by the strong immuno-regulatory mechanisms can lead to cancer progression. Therefore, it is crucial that the inevitable co-existence of these fundamental, yet conflicting roles of immune-regulatory cells is carefully streamlined as imbalances can be detrimental to the host. Infection with chronic persistent viruses is characterized by severe immune dysfunction resulting in T cell exhaustion and sometimes deletion of antigen-specific T cells. More often, this is due to increased immuno-regulatory processes, which are triggered to down-regulate immune responses and limit immunopathology. However, such heightened levels of immune disruption cause a concomitant loss of tumor immune-surveillance and create a permissive microenvironment for cancer establishment and progression, as demonstrated by increased incidences of cancer in immunosuppressed hosts. Paradoxically, while some cancers arise as a consequence of increased immuno-regulatory mechanisms that inhibit protective immune responses and impinge on tumor surveillance, other cancers arise due to impaired immuno-regulatory mechanisms and failure to limit pathogenic inflammatory responses. This intricate complexity, where immuno-regulatory cells can be beneficial in certain immune settings but detrimental in other settings underscores the need for carefully formulated interventions to equilibrate the balance between immuno-stimulatory and immuno-regulatory processes.