Compensatory Immune Suppression Following PD-1/PD-l1 Checkpoint Blockade in Ovarian Cancer
Technical Report,01 Sep 2016,31 Aug 2017
Mayo Clinic Jacksonville Jacksonville United States
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Ovarian cancer OC is highly immunogenic and generally speaking, higher lymphocytic infiltration is associated with better outcomes. Despite the presence of anti-tumor immune effectors, however, OCs overcome the immunologic onslaught by complex immune suppression strategies involving infiltration by a variety of specialized lymphoid or myeloid derived suppressor or regulatory cells andor the direct production and release of factors by the tumor into the tumor microenvironment. PD-1 and its ligands PD-L1 and PD-L2 constitute an important immune regulatory i.e. checkpoint pathway which suppresses or impairs effective T, B, and myeloid cell responses both in the initiation and effector phases of the immune response. This regulatory axis is widely thought to be important preventing autoimmunity during traditional immune responses, such as against infectious agents. Tumor regressions in response to PD-1PD-L1 blockade constitute a minor fraction of the objective responses which include disease stabilizations and minor regressions suggesting that there are biologic subsets of tumors that are more amendable to checkpoint blockade or, alternatively, tumors rapidly upregulate compensatory immune suppression mechanisms, following exposure to checkpoint blockade, that prevent their destruction.
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