Reversing Pro‐adhesive Niche Through Manipulating Aggregative Behaviors of Immune Cell Subsets With a Lubricous Janus Spray Gel for Enhancing Colorectal Cancer Postoperative Adjuvant Immunotherapy

ABSTRACT Tumor recurrence and postoperative adhesion represent prominent clinical challenges following surgical resection in colorectal cancer (CRC). However, these complications are often treated as discrete events, and their complex pathological crosstalk is frequently neglected, fueling a vicious cycle of adhesions and poor cancer prognoses. While postoperative adjuvant immunotherapies promote tumor eradication, the postoperative adhesion risk arising from indiscriminate immune infiltration remains underappreciated. Herein, a sprayable hydrogel (denoted as O‐Lipo@G‐GO) was engineered that reverses the proadhesive niche by acting as a lubricous Janus physical barrier while precisely modulating aggregated behaviors of immune cell subsets to enhance postoperative adjuvant immunotherapy in CRC. Specifically, O‐Lipo@G‐GO abrogated superaggregation of resident peritoneal GATA6 + macrophages (key adhesion precursors) through its lubricious interface and mannose ligand traps. Meanwhile, it promoted the canonical recruitment and activation of circulating immune cells by releasing immunoadjuvants and antigens. Such modulation of primary immune cell behavior balanced the double‐edged sword‐like effect of immunotherapy, circumventing proadhesive complications, eliciting durable antitumor immune responses, and suppressing adhesion‐related protumorigenic signals. Overall, O‐Lipo@G‐GO efficiently restrained residual and distant CT26 tumor growth, reduced lung metastasis, and achieved significant antiadhesion efficacy following intra‐abdominal surgery. Thus, it could serve as a straightforward yet potent intervention against postsurgical adhesions and CRC progression.