Post-surgical immune suppression: another target to improve postoperative outcomes

Uchida, Kanji

doi:10.1007/s00540-019-02651-3

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…In 2015, more than 80% of newly diagnosed cancers (15.2 million) required surgical resection 1 , and the number of new cases with surgical indications was continually increasing 2 . However, physical resection often results in immune suppression, which persists for weeks or even months as controlled by the healing process in the surgical wound 3 - 5 . This weakens the immune system and promotes tumor growth at both the primary and metastatic sites 4 , 6 .…”

Section: Introductionmentioning

confidence: 99%

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma

Gao,

Huang,

Jing

et al. 2024

Theranostics

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Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn 2+ ), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn 2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn 2+ -pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn 2+ -pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro : promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn 2+ -embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

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