Emerging evidence indicates that the Achilles' heel of cancer immunotherapies is often the complex interplay of tumor‐derived factors and deviant host properties, which involve a wide range of immune elements in the lymphoid and myeloid compartments. Regulatory lymphocytes, tumor‐conditioned myeloid‐derived suppressor cells (MDSCs), tumor‐associated macrophages, and dysfunctional and immature dendritic cells take part in a complex immunoregulatory network. Despite the fact that some mechanisms governing tumor‐induced immune tolerance and suppression are starting to be better understood and their complexity dissected, little is known about the diachronic picture of immune tolerance. Based on observations of MDSCs, we present a time‐structured and topologically consistent idea of tumor‐dependent tolerance progression in tumor‐bearing hosts.