Cancer immunoediting by the innate immune system in the absence of adaptive immunity
Timothy E. O’SullivanRobert Saddawi‐KonefkaWilliam VermiCatherine KoebelCora D. ArthurJ. Michael WhiteRavindra UppaluriDaniel M. AndrewsShin Foong NgiowMichele W.L. TengMark J. SmythRobert D. SchreiberJack D. Bui
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Abstract:
Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.Keywords:
Immunoediting
Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.
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Immunosuppression
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Abstract Cancer immunoediting is the process whereby immune cells protect against cancer formation and sculpt the immunogenicity of developing tumors. The complete process of immunoediting requires both innate and adaptive immunity, but it remains unclear to what extent innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3’methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2-/-, and RAG2-/-x γc-/- mice. We found that innate immune cells could indeed manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required γc and IFNγ, which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2-/-x γc-/- mice. Our results suggest that in the absence of adaptive immunity, natural killer cell production of IFNγ induces M1 macrophages, which act as important effectors during cancer immunoediting.
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Zoie immune system including innate immunity and adaptive immunity.Innate immune system is a general defense mechanism which is built up in the process of development and evolution of biological spe-cies,including tissue barrier function,cell-mediated immunity,and humor immunity.Innate immunocytes ale activated by the recognition of mode elements on the pathogen.The immunological effect is producedthronsh special signal transduction pathway:Earthworm belongs to invertebrate whose immune system lacks immunoglobulin and has not developed adaptive immunity.So earthworm protects itself tllrough innate immu-nity.
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Earthworm; Innate immunity; Nuelease
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Current dogma holds that the innate immune system primes the adaptive immune system in response to infection, which in turn amplifies innate responses in a positive loop to effectively control pathogens. Therefore, it is accepted in most cases that T-cell deficient hosts die of acute infection because of the impaired ability of the innate immune system to control pathogens. Recent studies, however, reveal that adaptive immune cells actively dampen initial innate responses. In contrast to current understanding, there is now evidence that an insufficient number of T cells results in loss of control of innate immune responses. This raises new questions regarding the, as of yet underappreciated, role of the adaptive immune system in early infection and inflammation.
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Summary: Although innate immunity evolved to combat pathogens, increasing awareness of a pivotal role in driving and shaping adaptive immunity has prompted this review on the role of innate immunity in graft rejection. We present evidence that grafts, especially xenografts, elicit innate responses, required for adaptive immunity. Particular attention is paid to studies by ourselves and others demonstrating the important role of innate immunity in T‐cell trafficking. The mechanisms by which grafts elicit innate immunity are a fertile subject for further investigation and an important target for therapeutic intervention.
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Intrinsic immunity
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CCL18
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Innate lymphoid cell
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Adaptive immune response or adaptive immunity is more advanced form of immunity, which is also called as 'acquired immune response' or 'delayed immune response' as it may take days to respond to the pathogens, but it is more persistent and effective. Two major types of cells play role in adaptive immune response viz. lymphocytes and antigen-presenting cells. Adaptive immunity is of two types- humoral immunity, mediated by B-lymphocytes involving antibodies and cell-mediated immunity, mediated by T-lymphocytes through cell-cell interaction. Adaptive immunity can be passive, when preformed antibodies are administered or active when the body of the person is sensitized to produce its own antibodies. The production of antibodies is based on identification of 'self' and 'non-self' cells. Sometimes the immune system may not respond suitably to the pathogen or may attack its own cells, such conditions lead to several immune dysfunctions including autoimmunity. Innate and adaptive immune responses interact with each other to provide necessary protection to the body.
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