Immune determinants of the pre-metastatic niche

Primary tumors actively and specifically prime pre-metastatic niches (PMNs), the future sites of organotropic metastasis, preparing these distant microenvironments for disseminated tumor cell arrival. While initial studies of the PMN focused on extracellular matrix alterations and stromal reprogramming, it is increasingly clear that the far-reaching effects of tumors are in great part achieved through systemic and local PMN immu-nosuppression. Here, we discuss recent advances in our understanding of the tumor immune microenviron-ment and provide a comprehensive overview of the immune determinants of the PMN's spatiotemporal evolution. Moreover, we depict the PMN immune landscape, based on functional pre-clinical studies as well as mounting clinical evidence, and the dynamic, reciprocal crosstalk with systemic changes imposed by cancer progression. Finally, we outline emerging therapeutic approaches that alter the dynamics of the interactions driving PMN formation and reverse immunosuppression programs in the PMN ensuring early anti-tumor immune responses.

Automated summary

Primary tumors actively induce immunosuppression in the pre-metastatic niche (PMN), the future sites of metastasis, to prepare for disseminated tumor cell arrival. This article discusses recent advances in understanding the tumor immune microenvironment and provides a comprehensive overview of the immune determinants of PMN's spatiotemporal evolution. The authors also outline emerging therapeutic approaches to alter PMN formation and reverse immunosuppression programs.