scholarly journals Elucidating tumor immunosurveillance and immunoediting: a comprehensive review

2021 ◽  
Vol 22 ◽  
Author(s):  
Estela Vieira de Souza Silva ◽  
Eduardo de Paula Nascente ◽  
Marina Pacheco Miguel ◽  
Carlos Eduardo Fonseca Alves ◽  
Veridiana Maria Brianezi Dignani de Moura

Abstract The action of the immune system against neoplastic diseases has become one of the main sources of research. The biological pathways of this system are known to contribute in limiting the progression and elimination of the tumor, and are delineated by concepts and mechanisms of immunosurveillance and immunoediting. Immunosurveillance is considered the process by which the immune system recognizes and inhibits the neoplastic process. The concept of immunoediting arises in the sense that immune system is able to shape the antigenic profile of the tumor due to selective pressure, based on the stages of tumor elimination, balance and evasion. The immune response occurs against tumor antigens and changes in the tumor microenvironment, involving different components of the innate immune system, such as T cells, natural Killer cells, B lymphocytes and macrophages. In this sense, knowing these concepts and understanding their respective mechanisms becomes essential in the investigation of new strategies for cancer prevention and cure. Thus, this review presents historical aspects and definitions of immunosurveillance and tumor immunoediting, with emphasis on its importance and applicability, such as on the different methods used in immunotherapy.

2019 ◽  
Author(s):  
Meghan A. Morrissey ◽  
Ronald D. Vale

SummaryMacrophages must engulf dead cells, debris, and pathogens, while selecting against healthy cells to prevent autoimmunity. Healthy cells express CD47 on their surface, which activates the SIRPA receptor on macrophages to suppress engulfment. Cancer cells overexpress CD47 to evade clearance by the innate immune system, making the CD47-SIRPA signaling axis an appealing therapeutic target. However, the mechanism by which CD47-SIRPA inhibits engulfment remains poorly understood. Here, we dissect SIRPA signaling using a reconstituted target with varying concentrations of activating and inhibitor ligands. We find that SIRPA is excluded from the phagocytic synapse between the macrophage and its target unless CD47 is present. Artificially directing SIRPA to the kinase-rich synapse in the absence of CD47 activates SIRPA and suppresses engulfment, indicating that the localization of the receptor is critical for inhibitory signaling. CD47-SIRPA inhibits integrin activation in the macrophage, reducing macrophage-target contact and suppressing phagocytosis. Chemical activation of integrins can override this effect and drive engulfment of CD47-positive targets, including cancer cells. These results suggest new strategies for overcoming CD47-SIRPA inhibition of phagocytosis with potential applications in cancer immunotherapy.


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