Microenvironment and Restore Immunosurveillance

Most of the events described above that happen in the tumor microenvironment are not observed if strong adaptive immunity exists against the aberrant forms of various tumor antigens. In highlighting the good, Dr. Jekyll side of these antigens, we discussed evidence of low immunity against these antigens could prevent tumor outgrowth and lead to long-term protective antitumor memory responses. Vaccination directed against certain TAAs can induce strong immune response that may mediate clearance of existing cancer foci and moreover, might be protective against new malignant transformation starting from a cancer stem cell. The presence of strong adaptive immunity in the tumor microenvironment can restore the balance between the proinflammatory responses of innate immune cells, that can be immunosuppressive and tumor promoting, and antitumor effector cells such as activated macrophage, T cells, NK cells and their cytokines.

Strong antitumor effector responses can be induced through vaccination with specific antigens and should be expected to change the tumor microenvironment such that it no longer supports tumor growth. The problem has been, that vaccines have been administered in the therapeutic setting where the tumor microenvironment is already fully established, immunosuppressive and tumor growth supportive. Even when effective immunity is generated, the effector cells do not function well once they arrive at the tumor site. The potential solution to this problem is to try to alter the tumor microenvironment prior to the application of immunotherapy. This can be accomplished by delivery of certain cytokines and chemokines [176-178] as well as by depletion of specific cell populations, such as Tregs [179]. Alternatively, induction of antitumor immune responses can be generated prophylactically in people at high risk for developing certain forms of cancer. These memory responses would get activated faster in response to early changes, such as new antigens on cancer stem cells and eliminate these cells before they have a chance to establish a tumor-promoting environment.

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