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Targeting the Immune System's Natural Response to Cell Death to Improve Therapeutic Response in Breast Cancers

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Technical Report,01 Jul 2013,30 Jun 2016

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Vanderbilt University Nashville United States

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We have proposed experiments to test the hypothesis that MerTK-mediated efferocytosis by tumor-associated macrophages TAMs is a major limitation to effective therapeutic responses, because efferocytosis of dying tumor cells drives production of wound-healingTh2-like cytokines, limits anti-tumor immunity, and promotes tumor growth. Two Aims were proposed to test this hypothesis. The goal of Aim 1 was to determine if MerTK-directed efferocytosis modulates cytokine expression, leukocyte infiltration, and growth of mouse mammary tumors, specifically testing the hypothesis that loss of MerTK would impair efferocytosis of dying tumor cells by TAMs, thus limiting production of Th2WH cytokines in the tumor microenvironmentTME, resulting in decreased tumor growth and metastasis. The goal of Aim 2 was to measure the impact of MerTK-directed efferocytosis on tumor re-emergence in therapeutically treated breast cancers, specifically testing the hypothesis that loss of MerTK-directed efferocytosis in the TME will limit Th2WH cytokines

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  • Medicine and Medical Research

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