基于量子点标记分子探针成像技术的肺癌转移微环境特征研究

The comprehensive overview of lung cancer progression suggests that the process is influenced by intrinsic properties of the tumor cells, as well as by tumor microenvironmental factors. The coevolution effects between cancer cells and tumor microenvironment determine the process of invasion and metastasis, which are the basic biological behaviors of lung cancer. Recognizing and identifying tumor microenvironment of metastasis would pave the way to illustrate the collective cell migration mode so as to better guide personal anti-angiogenic therapy in combination with radiotherapy. Our previous studies confirmed the heterogeneity of tumor neo-vessels in lung cancer tissues. And the more tumor neo-vessels distributed around the cancer cells and macrophages, the worse prognosis of cancer patients would be. Anti-angiogenic therapy could improve the efficacy of radiotherapy. Therefore, we propose that the tumor microenvironment of metastasis (TMEM), a unique spatial structure formed by cancer cells, macrophages and tumor neo-vessels in close vicinity with one another, could facilitate lung cancer metastasis. Based on these findings, this present study is aimed at accurate, sensitive and quantitative detection on TMEM based on quantum dots molecular probes and computer aided-digital imaging processing technology. The improvement of personal anti-angiogenic therapy based on TMEM could help develop innovative diagnosis and treatment strategy in combination radiotherapy with anti-angiogenic therapy in lung cancer.

侵袭转移是肺癌最本质的生物学特征，是癌细胞与微环境相互作用的结果。识别并鉴定肺癌转移微环境，明确群体侵袭转移模式，有助于个体化抗血管生成治疗，发挥阻断血道转移并放疗增敏的作用。我们前期研究证实肺癌组织中新生血管数量和分布异质，围绕在癌细胞和巨噬细胞周围的血管数量越多，预后越差，联合抗血管生成治疗可提高放疗疗效（NCT01218594）。由此我们推测癌细胞、巨噬细胞和血管共同构成的肺癌转移微环境，是肺癌群体侵袭转移的结构基础。本研究拟在前期研究基础上：发展基于量子点分子探针和数字图像处理技术的肺癌转移微环境分析平台，原位识别癌细胞、巨噬细胞、肿瘤新生血管的形态学及空间分布特征，定量计算肺癌转移微环境，揭示肺癌侵袭转移的集群特征；从临床组织标本验证肺癌转移微环境用于指导个体化抗血管生成治疗的效能，动物模型进一步验证并优化，为发展个体化抗血管生成治疗联合放疗的肺癌创新诊疗策略奠定理论基础。

侵袭转移是肺癌最本质的生物学特征，是癌细胞与微环境相互作用的结果。识别并鉴定肺癌转移微环境，明确群体侵袭转移模式，有助于个体化抗血管生成治疗，发挥阻断血道转移并放疗增敏的作用。我们前期研究证实肺癌组织中新生血管数量和分布异质，围绕在癌细胞和巨噬细胞周围的血管数量越多，预后越差，联合抗血管生成治疗可提高放疗疗效。由此我们推测癌细胞、巨噬细胞和血管共同构成的肺癌转移微环境，是肺癌群体侵袭转移的结构基础。本研究在前期研究基础上：构建肺癌数据库，并从已构建的肺癌数据库中选取具有完善临床病理信息的病例构建组织芯片，对肿瘤微环境进行成像及分析，证实肿瘤微环境关键成分PD-L1及TAMs的表达与NSCLC患者的预后密切相关，为肺癌个体化诊疗策略奠定理论基础。