肿瘤血管细胞或可帮助其逃脱机体的免疫监视

  来自卡若琳斯卡的研究者近日通过研究首次揭示，肿瘤血管中的细胞或可帮助创造一种局部环境来保护癌细胞免于被免疫细胞杀灭，相关研究结果刊登于国际杂志the Journal of the National Cancer Institute上，该研究或为开发更好的以免疫为基础的抗癌疗法提供思路。
  基于免疫的抗肿瘤疗法可以增强机体自身抵御癌症的能力，同样该领域也是近些年来研究者的关注焦点，当然研究者们在这一领域也取得了一些成就，尤其是针对恶性黑色素瘤的免疫疗法，然而仍然有很多患者对免疫为基础的疗法并无反应。而本文的研究结果则指出，肿瘤的外膜细胞，即肿瘤血管的一部分细胞，可以通过调节肿瘤局部环境来帮助癌细胞逃脱免疫监视。
  研究者Guillem Genove说道，揭示肿瘤外膜细胞、恶性细胞及免疫系统之间的相互作用或可帮助设计更多个体化及有效的癌症新型疗法。肿瘤往往会以多种机制来逃脱免疫系统的监视，而其中一种机制就是招募所谓的髓系来源抑制细胞(myeloid-derived suppressor cells，MDSCs)，这种细胞可以一直杀伤性T细胞破坏癌细胞的能力，众所周知，MDSCs存在的越多，癌症病人的预后或疗法反应就越差；肿瘤会分泌诸如白介素6（IL-6）等信号分子来帮助招募MDSCs，但IL-6肿瘤分泌背后的分子机制至今却并不清楚。
  研究者表示，肿瘤外膜细胞的数量越多，肿瘤微环境就显得越为正常，相反减少外膜细胞的数量则会改变肿瘤微环境，而且还和恶性细胞及更多MDSCs表达高水平IL-6直接相关；文章中研究者同时还鉴别出了携带较低水平外膜细胞及MDSCs水平升高的乳腺癌患者亚群，这些患者的预后较差，而且患者机体的肿瘤具有恶性的特点。
  最后研究者Genove说道，本文研究中我们发现增加肿瘤外膜细胞水平的途径或可帮助潜在降低IL-6的表达，这或许会改善毒性T细胞的活性以及引发机体更好地抗肿瘤效应。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Role of Tumor Pericytes in the Recruitment of Myeloid-Derived Suppressor Cells
JNCI   doi: 10.1093/jnci/djv209
JongWook Hong, Nicholas P. Tobin, Helene Rundqvist, Tian Li, Marion Lavergne, Yaiza García-Ibáñez, Hanyu Qin, Janna Paulsson, Manuel Zeitelhofer, Milena Z. Adzemovic, Ingrid Nilsson, Pernilla Roswall, Johan Hartman, Randall S. Johnson, Arne Östman, Jonas Bergh, Mirjana Poljakovic and Guillem Genové
Background: Pericytes are members of the tumor stroma; however, little is known about their origin, function, or interaction with other tumor components. Emerging evidence suggest that pericytes may regulate leukocyte transmigration. Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with powerful inhibitory effects on T-cell–mediated antitumor reactivity.

Methods: We generated subcutaneous tumors in a genetic mouse model of pericyte deficiency (the pdgfb ret/ret mouse) and littermate control mice (n = 6–25). Gene expression profiles from 253 breast cancer patients (stage I-III) were evaluated for clinic-pathological parameters and survival using Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) based on a two-sided Wald test.

Results: We report that pericyte deficiency leads to increased transmigration of Gr1+/CD11b+ cells in experimentally induced tumors. Pericyte deficiency produced defective tumor vasculature, resulting in a more hypoxic microenvironment promoting IL-6 upregulation in the malignant cells. Silencing IL-6 expression in tumor cells attenuated the observed differences in MDSC transmigration. Restoring the pericyte coverage in tumors abrogated the increased MDSC trafficking to pericyte-deficient tumors. MDSC accumulation in tumors led to increases in tumor growth and in circulating malignant cells. Finally, gene expression analysis from human breast cancer patients revealed increased expression of the human MDSC markers CD33 and S100A9 with concomitant decreased expression of pericyte genes and was associated with poor prognosis (HR = 1.88, 95% CI = 1.08 to 3.25, P = .03).

Conclusions: Our data uncovers a novel paracrine interaction between tumor pericytes and inflammatory cells and delineates the cellular events resulting in the recruitment of MDSC to tumors. Furthermore, we propose for the first time a role for tumor pericytes in modulating the expression of immune mediators in malignant cells by promoting a hypoxic microenvironment.