Abstract
Simple SummaryDespite great advances in the detailed profiling of tumor cells and the development of therapeutic agents, cancer metastasis is still a big hurdle in the treatment of cancer patients. This is possibly because tumor cells plastically evolve through interplay with the host environment, including stromal cells, vascular cells, and immune cells. The reciprocal evolution among the numerous components further increases the heterogeneity and complexity in both tumor cells and the host, leading to refractory cancer. It is important to better understand the entire metastatic cascade and the practical implementations targeting the oncoimmune drivers in the mechanisms. This review aims to boost the idea to break down the vicious spiral of the tumor–immunity aggravation more efficiently by combining some different agents in clinical settings.Residual metastasis is a major cause of cancer-associated death. Recent advances in understanding the molecular basis of the epithelial–mesenchymal transition (EMT) and the related cancer stem cells (CSCs) have revealed the landscapes of cancer metastasis and are promising contributions to clinical treatments. However, this rarely leads to practical advances in the management of cancer in clinical settings, and thus cancer metastasis is still a threat to patients. The reason for this may be the heterogeneity and complexity caused by the evolutional transformation of tumor cells through interactions with the host environment, which is composed of numerous components, including stromal cells, vascular cells, and immune cells. The reciprocal evolution further raises the possibility of successful tumor escape, resulting in a fatal prognosis for patients. To disrupt the vicious spiral of tumor–immunity aggravation, it is important to understand the entire metastatic process and the practical implementations. Here, we provide an overview of the molecular and cellular links between tumors’ biological properties and host immunity, mainly focusing on EMT and CSCs, and we also highlight therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients.
Highlights
Residual metastasis is a major cause of cancer-associated death
Epithelial tumor cells adhere to each other via tight junctions, but sometimes transform into mesenchymal types with low adhesive but high invasive properties in response to extrinsic stimuli, such as hypoxia and inflammation mediated by numerous factors, including WNT, NOTCH, transforming growth factor beta (TGFβ), epidermal growth factor (EGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and hypoxia inducible factor (HIF) within the tumor microenvironment [1,2]
Tumor-specific cytotoxic T cells (CTLs) are generated and activated through interaction between the T-cell receptor (TCR) and the major histocompatibility complex (MHC)–peptide complexes expressed on antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages [72]
Summary
Residual metastasis is a major cause of cancer-associated death. The epithelial–. Great progress in the molecular profiling of cancer EMT and the related cancer-initiated cells or cancer stem cells (CSCs) has defined the detailed characteristics, and the advances in understanding the molecular basis of EMT have revealed the landscapes of cancer metastasis, leading to the development of numerous treatments targeting the phenotypes and signaling pathways [5]. Immune checkpoint inhibitors (ICIs) have been considered to be a promising immunotherapeutic to knockout the immune underpinnings and have shown great therapeutic efficacies, long-lasting durable responses, even in patients with advanced and metastatic cancer [12]. To disrupt the vicious spiral of the tumor–immunity aggravation leading to cancer metastasis, it is important to better understand both the entire metastatic cascade and the clinical implementation. We highlight the molecular and cellular links between the tumor biology and host immunity on the basis of cancer metastasis and provide an overview of the therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients
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