Targeting Myeloid-Derived Suppressor Cells for Premetastatic Niche Disruption After Tumor Resection
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REVIEW ARTICLE – TRANSLATIONAL RESEARCH
Targeting Myeloid-Derived Suppressor Cells for Premetastatic Niche Disruption After Tumor Resection Fan Tang, MD, PhD1,2, Yan Tie, MD, PhD3, Weiqi Hong, PhD1, Yuquan Wei, MD, PhD1, Chongqi Tu, MD2, and Xiawei Wei, PhD1 1
Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2 Department of Orthopeadics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3 Department of Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China
ABSTRACT Surgical resection is a common therapeutic option for primary solid tumors. However, high cancer recurrence and metastatic rates after resection are the main cause of cancer related mortalities. This implies the existence of a ‘‘fertile soil’’ following surgery that facilitates colonization by circulating cancer cells. Myeloid-derived suppressor cells (MDSCs) are essential for premetastatic niche formation, and may persist in distant organs for up to 2 weeks after surgery. These postsurgical persistent lung MDSCs exhibit stronger immunosuppression compared with presurgical MDSCs, suggesting that surgery enhances MDSC function. Surgical stress and trauma trigger the secretion of systemic inflammatory cytokines, which enhance MDSC mobilization and proliferation. Additionally, damage associated molecular patterns (DAMPs) directly activate MDSCs through pattern recognition receptor-mediated signals. Surgery also increases vascular permeability, induces an increase in lysyl oxidase and extracellular matrix remodeling in lungs, that enhances MDSC mobilization. Postsurgical therapies that inhibit the induction of premetastatic niches by MDSCs promote the long-term survival of patients. Cyclooxygenase-2
Ó The Author(s) 2020 First Received: 7 August 2020 Accepted: 29 October 2020 C. Tu, MD e-mail: [email protected] X. Wei, PhD e-mail: [email protected]
inhibitors and b-blockade, or their combination, may minimize the impact of surgical stress on MDSCs. AntiDAMPs and associated inflammatory signaling inhibitors also are potential therapies. Existing therapies under tumorbearing conditions, such as MDSCs depletion with lowdose chemotherapy or tyrosine kinase inhibitors, MDSCs differentiation using all-trans retinoic acid, and STAT3 inhibition merit clinical evaluation during the perioperative period. In addition, combining low-dose epigenetic drugs with chemokine receptors, reversing immunosuppression through the Enhanced Recovery After Surgery protocol, repairing vascular leakage, or inhibiting extracellular matrix remodeling also may enhance the long-term survival of curative resection patients.
Surgical resection is a common therapeutic option for malignant solid tumors. However, recurrence and me
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