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 inhibitors and β-blockade, or their combination, may minimize the impact of surgical stress on MDSCs. Anti-DAMPs and associated inflammatory signaling inhibitors also are potential
therapies. Existing
therapies under
tumor-bearing conditions, such as MDSCs depletion with low-dose
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.