The complexity of immune evasion mechanisms throughout the metastatic cascade

Metastasis, the spread of cancer from a primary site to distant organs, is an important challenge in oncology. This Review explores the complexities of immune escape mechanisms used throughout the metastatic cascade to promote tumor cell dissemination and affect organotropism. Specifically, we focus on adaptive plasticity of disseminated epithelial tumor cells to understand how they undergo phenotypic transitions to survive microenvironmental conditions encountered during metastasis. The interaction of tumor cells and their microenvironment is analyzed, highlighting the local and systemic effects that innate and adaptive immune systems have in shaping an immunosuppressive milieu to foster aggressive metastatic tumors. Effectively managing metastatic disease demands a multipronged approach to target the parallel and sequential mechanisms that suppress anti-tumor immunity. This management necessitates a deep understanding of the complex interplay between tumor cells, their microenvironment and immune responses that we provide with this Review. This Review on the interplay between the immune system and metastasis is part of our wider Series of Reviews on Cancer Immunology and Immunotherapy.