Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, United States.
Cancer Lett. 2012 Nov 1;324(1):91-7. doi: 10.1016/j.canlet.2012.05.002. Epub 2012 May 8.
Tumor microenvironment contributes to a large extent for failure of immunological destruction of antigenic tumors. Most solid tumors adapt to the microenvironment and escape the host immune system. The dramatic and systemic effectiveness of neuro-immune ligand Capsaicin (CP) in regression of established solid tumors led us to investigate its immunomodulatory role in tumor microenvironment. In this report we demonstrate that CP induced tumor cell apoptosis leads to increased sensitization of the surrounding stroma manifested by enhanced antigen presentation by stromal macrophages and its destruction by tumor specific T-cells. Further, CP injection alters the tumor microenvironment with regards to tumor-infiltrating Treg cells as well as the cytokine milieu at the tumor site. Our data collectively demonstrates that injection of CP sets in motion, a cascade of several independent innate and adaptive immunological events initiated at the tumor environment.
肿瘤微环境在很大程度上导致了抗原性肿瘤的免疫破坏失败。大多数实体瘤适应微环境并逃避宿主免疫系统。神经免疫配体辣椒素（Capsaicin，CP）在消退已建立的实体瘤方面具有显著和系统性的效果，促使我们研究其在肿瘤微环境中的免疫调节作用。在本报告中，我们证明 CP 诱导的肿瘤细胞凋亡导致周围基质的敏感性增强，表现为基质巨噬细胞增强抗原呈递及其被肿瘤特异性 T 细胞破坏。此外，CP 注射改变了肿瘤微环境，包括肿瘤浸润性 Treg 细胞以及肿瘤部位的细胞因子环境。我们的数据综合表明，CP 的注射引发了一系列独立的先天和适应性免疫事件，这些事件始于肿瘤环境。
