Abascal Jensen, Oh Michael S, Liclican Elvira L, Dubinett Steven M, Salehi-Rad Ramin, Liu Bin
Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, USA.
Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Cells. 2023 Oct 4;12(19):2404. doi: 10.3390/cells12192404.
Non-small-cell lung cancer (NSCLC) remains one of the leading causes of death worldwide. While NSCLCs possess antigens that can potentially elicit T cell responses, defective tumor antigen presentation and T cell activation hinder host anti-tumor immune responses. The NSCLC tumor microenvironment (TME) is composed of cellular and soluble mediators that can promote or combat tumor growth. The composition of the TME plays a critical role in promoting tumorigenesis and dictating anti-tumor immune responses to immunotherapy. Dendritic cells (DCs) are critical immune cells that activate anti-tumor T cell responses and sustain effector responses. DC vaccination is a promising cellular immunotherapy that has the potential to facilitate anti-tumor immune responses and transform the composition of the NSCLC TME via tumor antigen presentation and cell-cell communication. Here, we will review the features of the NSCLC TME with an emphasis on the immune cell phenotypes that directly interact with DCs. Additionally, we will summarize the major preclinical and clinical approaches for DC vaccine generation and examine how effective DC vaccination can transform the NSCLC TME toward a state of sustained anti-tumor immune signaling.
非小细胞肺癌(NSCLC)仍然是全球主要的死亡原因之一。虽然NSCLC具有可能引发T细胞反应的抗原,但有缺陷的肿瘤抗原呈递和T细胞活化会阻碍宿主的抗肿瘤免疫反应。NSCLC肿瘤微环境(TME)由可促进或对抗肿瘤生长的细胞和可溶性介质组成。TME的组成在促进肿瘤发生和决定对免疫疗法的抗肿瘤免疫反应方面起着关键作用。树突状细胞(DC)是激活抗肿瘤T细胞反应并维持效应反应的关键免疫细胞。DC疫苗接种是一种有前景的细胞免疫疗法,有可能通过肿瘤抗原呈递和细胞间通讯促进抗肿瘤免疫反应并改变NSCLC TME的组成。在这里,我们将综述NSCLC TME的特征,重点关注与DC直接相互作用的免疫细胞表型。此外,我们将总结DC疫苗生成的主要临床前和临床方法,并研究有效的DC疫苗接种如何将NSCLC TME转变为持续抗肿瘤免疫信号状态。