Tumor dissemination and metastasis are fatal to cancer patients due to its high incidence and mortality. In the metastatic process, epithelial-mesenchymal transition (EMT) has been considered as a pivotal biological program to transform tumor cells into a mesenchymal type with high invasive and metastatic property and anti-apoptotic and dormant cancer stem-like property leading to treatment resistance. The great advances in understanding the genomic, proteomic, microenvironmental, and immunological mechanisms underlying cancer metastasis have revealed its landscape and have led to clinical development of many agents targeting the identified molecular and cellular networks. However, the therapeutic efficacy is relatively low in many cases, and prevention and elimination of the disseminated tumor cells remain to be fully achieved in clinical settings. The strongest reason is the tumor plasticity that constantly produces diversity through the evolutional changes receiving extrinsic modification with its surrounding environment composed of an abundance of elements, such as stromal cells, vascular cells, immune cells, and cytokines and chemokines produced from these cells, in the host. The interaction among all elements in an unrelenting manner enormously increases heterogeneity and complexity in both tumor cells and immunity, and the host immunity finally allows the tumor to escape due to its exhaustion and dysfunction. All these vastly facilitate tumor metastasis leading to refractory cancer. Thus, it is important to spoil the tumor-immunity reciprocal evolution. Here, we highlight the immunological components that facilitate tumor dissemination and metastasis and overview the practical treatments targeting the immune allies to cancer metastasis for successfully treating cancer.

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Immune Allies to Cancer Metastasis

  • Chie Kudo-Saito

摘要

Tumor dissemination and metastasis are fatal to cancer patients due to its high incidence and mortality. In the metastatic process, epithelial-mesenchymal transition (EMT) has been considered as a pivotal biological program to transform tumor cells into a mesenchymal type with high invasive and metastatic property and anti-apoptotic and dormant cancer stem-like property leading to treatment resistance. The great advances in understanding the genomic, proteomic, microenvironmental, and immunological mechanisms underlying cancer metastasis have revealed its landscape and have led to clinical development of many agents targeting the identified molecular and cellular networks. However, the therapeutic efficacy is relatively low in many cases, and prevention and elimination of the disseminated tumor cells remain to be fully achieved in clinical settings. The strongest reason is the tumor plasticity that constantly produces diversity through the evolutional changes receiving extrinsic modification with its surrounding environment composed of an abundance of elements, such as stromal cells, vascular cells, immune cells, and cytokines and chemokines produced from these cells, in the host. The interaction among all elements in an unrelenting manner enormously increases heterogeneity and complexity in both tumor cells and immunity, and the host immunity finally allows the tumor to escape due to its exhaustion and dysfunction. All these vastly facilitate tumor metastasis leading to refractory cancer. Thus, it is important to spoil the tumor-immunity reciprocal evolution. Here, we highlight the immunological components that facilitate tumor dissemination and metastasis and overview the practical treatments targeting the immune allies to cancer metastasis for successfully treating cancer.