Biomark Res. 2026 Jul 3. doi: 10.1186/s40364-026-00957-5. Online ahead of print.
ABSTRACT
Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectiveness is often limited by inadequate tumor-site specificity, systemic toxicity, poor immune cell trafficking, and tumor heterogeneity. Consequently, a critical unmet clinical need persists for biologically precise strategies capable of eliminating residual tumor cells at their point of vulnerability. Platelets, traditionally viewed as mediators of hemostasis, are now recognized as active regulators of tumor progression. By facilitating fibrin deposition, shielding circulating tumor cells from immune attack, and shaping inflammatory networks, platelets inadvertently support the survival of postoperative tumors. Paradoxically, these same wound-targeting properties create a compelling therapeutic opportunity: leveraging platelet-driven homing mechanisms to direct immunotherapy precisely to fibrin-rich surgical beds where recurrence often originates. In this review, we propose a platelet-guided CAR-T platform that leverages endogenous wound biology to create a precision immunotherapeutic delivery system. This strategy integrates platelet membrane cloaking or platelet-CAR-T conjugation with thrombin-responsive biomaterial depots to enhance local effector retention, amplify effector-to-target ratios, and prolong functional persistence. Programmable safety features, including affinity tuning, logic-gated activation, and inducible suicide switches, are used to reduce thrombo-inflammatory risk while preserving therapeutic efficacy. These mechanisms restrict activity to appropriate contexts and allow controlled shutdown in case of adverse events, improving overall safety. When coupled with minimal residual disease-guided patient selection using circulating biomarkers, this approach establishes a clinically actionable framework for perioperative intervention. Emerging preclinical evidence suggests that localized platelet-assisted delivery can reduce circulating tumor cell burden, enhance antigen presentation when combined with immune adjuvants, and suppress recurrence more effectively than systemic therapies. With rigorous safety validation, scalable manufacturing, and biomarker-enriched clinical trials, platelet-guided CAR-T therapy has the potential to transform the postoperative microenvironment from a sanctuary of tumor survival into a targeted domain for durable immune-mediated eradication.Clinical trial numberNot applicable.
PMID:42400102 | DOI:10.1186/s40364-026-00957-5