Departments of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, United States.
Front Immunol. 2019 Feb 15;10:193. doi: 10.3389/fimmu.2019.00193. eCollection 2019.
In recent decades, there has been substantial growth in our understanding of the immune system and its role in tumor growth and overall survival. A central finding has been the cross-talk between tumor cells and the surrounding environment or stroma. This tumor stroma, comprised of various cells, and extracellular matrix (ECM), has been shown to aid in suppressing host immune responses against tumor cells. Through immunosuppressive cytokine secretion, metabolic alterations, and other mechanisms, the tumor stroma provides a complex network of safeguards for tumor proliferation. With recent advances in more effective, localized treatment, radiation therapy (XRT) has allowed for strategies that can effectively alter and ablate tumor stromal tissue. This includes promoting immunogenic cell death through tumor antigen release to increasing immune cell trafficking, XRT has a unique advantage against the tumoral immune evasion mechanisms that are orchestrated by stromal cells. Current studies are underway to elucidate pathways within the tumor stroma as potential targets for immunotherapy and chemoradiation. This review summarizes the effects of tumor stroma in tumor immune evasion, explains how XRT may help overcome these effects, with potential combinatorial approaches for future treatment modalities.
近几十年来，我们对免疫系统及其在肿瘤生长和整体生存中的作用有了实质性的认识。一个中心发现是肿瘤细胞与其周围环境或基质之间的相互作用。这种肿瘤基质由各种细胞和细胞外基质（ECM）组成，已被证明有助于抑制宿主对肿瘤细胞的免疫反应。通过免疫抑制性细胞因子分泌、代谢改变和其他机制，肿瘤基质为肿瘤增殖提供了一个复杂的保护网络。随着更有效、局部治疗的最新进展，放射治疗（XRT）允许采取策略有效地改变和消融肿瘤基质组织。这包括通过肿瘤抗原释放促进免疫原性细胞死亡，增加免疫细胞的迁移，XRT 对由基质细胞协调的肿瘤免疫逃逸机制具有独特的优势。目前正在进行研究，以阐明肿瘤基质中的途径作为免疫治疗和放化疗的潜在靶点。这篇综述总结了肿瘤基质在肿瘤免疫逃逸中的作用，解释了 XRT 如何有助于克服这些作用，以及未来治疗方式的潜在联合方法。
