Over the past decade, immunotherapy has emerged as the fourth pillar of cancer therapy, following surgery, chemotherapy, and radiotherapy. However, tumors often evade immune responses by altering the tumor microenvironment (TME), which recruits immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages, and regulatory T cells. Among these, MDSCs are considered key contributors to immunotherapy failure and have become major targets in new therapeutic strategies. Growing evidence indicates that controlling MDSCs is critical to the success of cancer immunotherapy, and several drug classes have shown feasibility. In this review, we introduce the significance of MDSCs as a target in cancer immunotherapy and highlight different therapeutic approaches to counteract their immunosuppressive functions. We discuss recent efforts to optimize drug delivery for controlling MDSCs, focusing on resiquimod (R848) as a representative drug candidate.
He et al. (2026) studied this question.