Targeting Oncoimmune Drivers of Cancer Metastasis

SIMPLE SUMMARY: Despite 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. ABSTRACT: 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.