Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

摘要

class="head no_bottom_margin" id="sec1title">IntroductionCells dying by apoptosis are rapidly engulfed by phagocytes. Histologically, apoptotic cells are most commonly co-localized with macrophages, and the phagocytic response is accompanied by production of anti-inflammatory and trophic factors []. Similar tissue-reparatory activation states are typical of tumor-associated macrophages (TAMs), and there is growing recognition that TAMs often promote tumor growth and progression by facilitating angiogenesis, matrix remodeling, and metastasis and by suppressing anti-tumor immunity. Thus, TAM accumulation and activation are generally associated with poor prognosis. The pro-tumor properties of TAMs have been studied extensively in certain malignancies [], but the mechanisms underlying oncogenic activation of TAMs are not fully understood.Apoptosis has a defined purpose in preventing tumorigenesis [], but, paradoxically, high incidence of apoptosis is linked to aggressive disease in multiple malignancies []. Indeed, cell loss is significant in aggressive tumors [], and it is notable that programmed cell death can generate reparative and regenerative tissue responses such as angiogenesis and compensatory proliferation that have strong potential to be causally associated with tumor progression [].Given the poor prognostic indications of both apoptosis and TAM content in malignant disease and the established functional relationship between apoptosis and macrophage activation, we hypothesized that loss of tumor cells by apoptosis and associated macrophage activation could facilitate progression of malignant disease. Here, we show that apoptosis promotes tumor growth, angiogenesis, and accumulation of pro-oncogenic TAMs in aggressive non-Hodgkin’s lymphoma (NHL).