AACR Special Conference on Tumor Microenvironment Complexity: Emerging Roles in C

描述(申请人提供)：在过去的十年里，人们越来越认识到，肿瘤的非恶性成分，称为肿瘤微环境(TME)，在癌症的发生和进展1-4中发挥着重要的贡献作用。这种对癌症的异型观点认识到，肿瘤细胞可能本质上不能传播或抵抗治疗性侮辱，但由于与微环境的特定相互作用，可以获得这些特性。物理微环境条件，如缺氧和酸中毒5，与细胞外基质(ECM)6的黏附，生长因子，促炎细胞因子和趋化因子7，肿瘤相关的成纤维细胞和内皮细胞，先天和适应性免疫细胞以及肿瘤相关的巨噬细胞，在癌症从恶性转化到转移和抵抗治疗的所有阶段都有作用。自从上世纪90年代末S主要关注细胞外基质和血管生成之后，我们对微环境影响肿瘤进展的机制的了解以指数级的速度增长。我们更好地理解了肿瘤微环境的复杂性及其在癌症进展中的作用，并看到了许多新概念的出现(图1)。例如，已经很好地证明了骨髓来源的细胞有助于肿瘤血管生成和促进转移的生态位的建立。我们现在充分认识到，免疫系统可以极化的方式抑制或促进癌症进展，巨噬细胞在转移中发挥重要作用。我们更好地了解了肿瘤微环境促进治疗耐药性的机制8。因此，这是这一领域特别令人兴奋的时刻，因为我们的知识达到了临界点，开始转化为新的治疗方式。在本申请中，我们请求支持将于2011年11月3-6日在佛罗里达州奥兰多的希尔顿奥兰多酒店举行的“肿瘤微环境复杂性：癌症治疗中的新角色”会议。 公共卫生相关性：随着我们开始了解肿瘤微环境如何影响肿瘤的发生、发展、转移和对治疗的抵抗力，我们更好地利用这些知识将其转化为新的治疗方式。这次及时召开会议的目的是召集该领域的专家和更多的初级科学家讨论这些新出现的概念，审查它们在翻译方面的重要性，并确定该领域中应作为进一步调查重点的其他领域。

DESCRIPTION (provided by applicant): Over the last decade it has become increasingly recognized that non-malignant components of a tumor, called the tumor microenvironment (TME), play a major contributor role in cancer development and progression 1-4. This heterotypic view of cancer recognizes that tumor cells which may not be intrinsically able to disseminate or to resist therapeutic insults, can acquire these properties as the result of specific interactions with the microenvironment. Physical microenvironmental conditions such as hypoxia and acidosis 5, adhesion to the extracellular matrix (ECM) 6, growth factors, pro-inflammatory cytokines and chemokines 7, carcinoma- associated fibroblasts and endothelial cells, innate and adaptative immune cells and tumor-associated macrophages contribute to all stages of cancer progression from malignant transformation to metastasis and resistance to therapy. After having a primary focus on the extracellular matrix (ECM) and on angiogenesis in the late 1990's, our knowledge of the mechanisms by which the microenvironment affects tumor progression has grown at an exponential rate. We appreciate better the complexity of the tumor microenvironment and its role in cancer progression and have seen many new concepts emerging (Figure 1). For example, it is well demonstrated that bone marrow-derived cells contribute to tumor vasculogenesis and to the establishment of the pro-metastatic niche. We now fully realize that the immune system can be polarized in a manner that suppresses or promotes cancer progression and that macrophages play an essential role in metastasis. We understand better the mechanism by which the tumor microenvironment promotes therapeutic resistance 8. It is therefore a particularly exciting time in this field, as our knowledge reaches the critical point when it begins to translate into new therapeutic modalities. In this application we are requesting support for a conference on "Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy" to be held November 3-6, 2011 at the Hilton Orlando Hotel, Orlando, FL. PUBLIC HEALTH RELEVANCE: As we begin to understand how the tumor microenvironment can influence tumor initiation, progression, metastasis, and resistance to therapy, we are better equipped to utilize this knowledge for translation into new therapeutic modalities. The purpose of this timely conference is to bring together experts in the field and more junior scientists to discuss these emerging concepts, to examine their translational importance, and to identify other areas in the field that should be the focus of further investigation.