Targeting splenic myeloid cells synergizes with CD47 blockade to inhibit postsurgical tumor recurrence and metastasis

Area of Science:

• Immunology
• Nanomedicine
• Oncology

Background:

• Cancer recurrence and metastasis are primary causes of mortality in solid tumors.
• Depleting tumor-associated myeloid cells has shown limited clinical success due to compensatory mechanisms.
• The spleen continuously supplies myeloid cells that support tumor progression.

Purpose of the Study:

• To explore spleen-targeted immune cell reprogramming as a strategy to prevent postoperative cancer recurrence and metastasis.
• To investigate the potential of a novel spleen-targeted nanosystem for inducing trained immunity in myeloid cells.
• To evaluate the synergistic effects of the nanosystem combined with anti-CD47 therapy.

Main Methods:

• Development of a spleen-targeted nanosystem (MDP@AE-lip) integrating apolipoprotein, erythrocyte membranes, and PLGA.
• Utilizing an orthotopic breast cancer model to study tumor progression and splenic immune microenvironment changes.
• Assessing the induction of trained immunity via epigenetic and metabolic remodeling of splenic myeloid cells.
• Combining the nanosystem with anti-CD47 therapy to evaluate combined antitumor efficacy.

Main Results:

• Tumor progression was found to reshape the splenic immune microenvironment, increasing myeloid cells with myeloid-derived suppressor cell (MDSC)-like characteristics.
• The MDP@AE-lip nanosystem efficiently accumulated in the spleen and engaged splenic immune cells.
• The combined therapy reduced postoperative recurrence by 60% and delayed metastasis.
• MDP@AE-lip induced trained immunity through epigenetic and metabolic remodeling of splenic myeloid cells.

Conclusions:

• Reprogramming splenic myeloid cells via targeted nanomedicine represents a promising strategy to combat cancer recurrence and metastasis.
• Spleen-targeted immune activation can synergistically enhance innate and adaptive antitumor responses.
• This approach holds significant potential for clinical translation in preventing postoperative tumor spread.