Long noncoding RNA: a dazzling dancer in tumor immune microenvironment
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(2020) 39:231
REVIEW
Open Access
Long noncoding RNA: a dazzling dancer in tumor immune microenvironment Yalu Zhang†, Qiaofei Liu† and Quan Liao*
Abstract Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations. Keywords: LncRNA, Tumor immune microenvironment, Cancer immunotherapy
Background Cancer is not a chaotic malignant cell mass, but a delicate “hostile” organ, where many other cells are recruited and domesticated to become “accomplices”, thereby protecting themselves from recognition and attack by the immune system [1]. In addition to tumor cells, there are also important stromal components in tumor niche. The stroma is composed of substantial cells, including epithelial, fat, fibroblasts, smooth muscle, vascular, and immune cells along with the extracellular matrix (ECM) and abundant signaling molecules (Fig. 1) [2]. Together, they form the microenvironment in which the tumor is located, namely tumor microenvironment (TME). Besides, TME exhibits aberrant physiological conditions, like hypoxia, acidic extracellular pH and elevated interstitial fluid pressure, due to the malformed tumor vessels. The TME is an intricate physical and biochemical system that plays a significant role in tumor initiation, growth, distant metastasis, and affect the * Correspondence: [email protected] † Yalu Zhang and Qiaofei Liu are the co-first authors. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Shuaifuyuan 1, Dongcheng District, 100730 Beijing, China
outcome of treatments [1, 2]. Among the components of TME, distinct populations of innate and adaptive immune cells consist of tumor immune microenvironment (TIME). TIME primarily consists of myeloid cells, lymphocytes and some other innate immune cells. Myeloid cells comprise macrophages, neutrophils, myeloid derived suppressor cells (MDSCs); lymphocytes include B cells, CD4+ T helper (Th) cells, regulatory T cells (Tregs), CD8+ cytotoxic T lymphocytes (CTLs); and the innate immune cells contain natural killer (NK) cells and dendritic cells (DCs) (Fig. 1). TIME influences the immune escape of cancer, the response to immunotherapy, and the survival rate of patients. In the human genome, about 93% of DNA can be transcribed into RNA, of which only 2% are proteincodi
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