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The review explains why controlling MDSCs matters for successful immunotherapy and summarizes therapeutic approaches designed to counteract MDSC-mediated immunosuppression, with emphasis on drug-delivery optimization using resiquimod (R848).",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/drug-delivery-systems-for-resiquimod-to-control-myeloid-derived-suppressor-cells-in-cancer-immunotherapy/355250/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/drug-delivery-systems-for-resiquimod-to-control-myeloid-derived-suppressor-cells-in-cancer-immunotherapy/355250.png","ImageObject",300,407,{"name":42,"@type":43},"Genevieve","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why 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Myeloid-Derived Suppressor Cells in Cancer Immunotherapy  \nYanying He1 | Yoon Yeo1,2,3  \n1Department of Industrial and Molecular Pharmaceutics, Purdue University, West Lafayette, Indiana, USA | 2Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA | 3Purdue University Institute for Cancer Research, West Lafayette, Indiana, USA  \nCorrespondence: Yoon Yeo ([yyeo@purdue.edu](yyeo@purdue.edu))  \nReceived: 19 November 2025 | Revised: 21 January 2026 | Accepted: 28 January 2026  \nChief Editor: Fabiana Quaglia | Academic Editor: Olivia M Merkel  \nKeywords: cancer immunotherapy | drug delivery | immunosuppression | myeloid-derived immunosuppressor cells | resiquimod | TLR7 agonist  \nABSTRACT  \nOver 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.  \n1 | Introduction  \nCancer remains one of the most significant public health challenges worldwide. Approximately 20 million cases are diagnosed, and nearly 10 million cancer-related deaths occur worldwide every year (Bray et al. 2024) . Notably, lung cancer continues to be the leading cause of cancer death, with an estimated 1.8 million deaths, accounting for one-fifth of the cancer deaths, followed closely by colorectal, liver, breast, and stomach cancers (Bray et al. 2024) . Cancer control has relied on three therapeutic pillars in the previous 60 years: surgery, chemotherapy, and radiotherapy (Yuzhalin 2024) . These modalities, as well as continuously developing combinational therapies, have improved patient survival.  \nMeanwhile, immunotherapy has emerged over the past decade as the fourth pillar of cancer immunotherapy. Immunotherapy  \nleverages the body's innate and adaptive immune system to combat cancer cells, based on immune-activating cytokines or small molecules, immune-checkpoint blockade (ICB), adoptive cell transfer, and therapeutic cancer vaccines (Hunter 2017) . Various immune checkpoint inhibitors, preventing PD-1/PDL1 or CTLA-4 from inactivating cytotoxic T cells, have been approved for clinical use in the 2010s for treating dozens of tumor types (Lee et al. 2022) . Adoptive transfer of chimeric antigen receptor T (CAR-T) cells was approved for the treatment of hematologic malignancies (Ikeda 2025) . CAR-T cells are engineered to target tumor surface antigen, such as CD19 or B-cell maturation antigen (BCMA) . In 2024, the US Food and Drug Administration approved the first tumor-infiltrating lymphocyte (TIL) therapy, Lifileucel (Amtagvi), autologous tumor-specific T cells. TILs are extracted from a patient, expanded ex vivo, and reinfused to the patient, for the treatment of PD-1-refractory metastatic melanoma (Kaur et al. 2025) .  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2026 The Author(s). WIREs Nanomedicine and Nanobiotechnology published by","cbCaic7hmbnJXQt9","https://ap.wps.com/l/cbCaic7hmbnJXQt9","pdf",3488870,31,"English","# Abstract\n# Introduction\n## Cancer as a global public health challenge\n## Immunotherapy as the fourth pillar of cancer therapy\n## Immune checkpoint blockade and adoptive cell transfer\n## Tumor microenvironment and immunosuppressive cells (MDSCs, TAMs, Tregs)\n# Drug Delivery Systems Targeting MDSCs (Resiquimod Focus)","[{\"question\":\"Why are myeloid-derived suppressor cells (MDSCs) important in cancer immunotherapy failure?\",\"answer\":\"MDSCs are described as major contributors to immunotherapy failure because they suppress other immune cells and expand immunosuppressive populations within the tumor microenvironment.\"},{\"question\":\"What does the review propose as a strategy to improve immunotherapy outcomes?\",\"answer\":\"The review emphasizes controlling MDSCs and outlines therapeutic approaches aimed at counteracting their immunosuppressive functions, including optimizing drug delivery.\"},{\"question\":\"Why is resiquimod (R848) specifically discussed?\",\"answer\":\"Resiquimod is presented as a representative drug candidate, and the review focuses on recent efforts to optimize drug delivery systems for controlling MDSCs using this candidate.\"}]","Drug Delivery Systems for Resiquimod to Control Myeloid-Derived Suppressor Cells in Cancer Immunotherapy | PDF",1790117131,78]