{"paper_id":"75317f07-9e52-49a8-bce3-8260b47e80a6","body_text":"Abstract\nPostoperative 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.\nClinical trial number\nNot applicable.\nHighlights\nIdentifies the postoperative fibrin-rich niche as a transient, targetable reservoir for microscopic residual disease.\nIntroduces platelet-guided CAR-T delivery via membrane cloaking or platelet–T cell conjugation with thrombin-responsive biomaterial depots.\nEnables spatially confined immune activation within the perioperative fibrin scaffold.\nIntegrates programmable safety circuits (affinity tuning, logic gating, suicide switches) to limit systemic toxicity and thromboinflammation.\nProposes MRD-guided perioperative stratification using ctDNA and circulating biomarkers.\nDemonstrates preclinical enhancement of local effector function, reduced tumor dissemination, and superior recurrence control.\nDefines a translational roadmap spanning GLP safety profiling, GMP platelet engineering, and biomarker-enriched adaptive trials.\nAbstractSection Graphical AbstractSimilar content being viewed by others\nAbbreviations\n- AhR:\n-\nAryl hydrocarbon receptor\n- APC:\n-\nAntigen-presenting cell\n- ASS1:\n-\nArgininosuccinate synthase-1\n- CAR:\n-\nChimeric antigen receptor\n- CAR-T:\n-\nChimeric antigen receptor T cells\n- CPT1:\n-\nCarnitine palmitoyltransferase-1\n- CRS:\n-\nCytokine release syndrome\n- CTC:\n-\nCirculating tumor cell\n- ctDNA:\n-\nCirculating tumor DNA\n- ECM:\n-\nExtracellular matrix\n- FAO:\n-\nFatty-acid oxidation\n- FASN:\n-\nFatty-acid synthase\n- FGF:\n-\nFibroblast growth factor\n- GLP:\n-\nGood Laboratory Practice\n- GLS:\n-\nGlutaminase\n- GMP:\n-\nGood Manufacturing Practice\n- GM-CSF:\n-\nGranulocyte-macrophage colony-stimulating factor\n- HAP:\n-\nHypoxia-activated prodrug\n- HER2:\n-\nHuman epidermal growth factor receptor-2\n- HIF:\n-\nHypoxia-inducible factor\n- HK2:\n-\nHexokinase-2\n- ICI:\n-\nImmune checkpoint inhibitor\n- IDO1:\n-\nIndoleamine-2,3-dioxygenase-1\n- IFN-γ:\n-\nInterferon-gamma\n- IL-6:\n-\nInterleukin-6\n- LDH/LDHA:\n-\nLactate dehydrogenase A\n- MCT:\n-\nMonocarboxylate transporter\n- MRD:\n-\nMinimal residual disease\n- NET:\n-\nNeutrophil extracellular trap\n- NK:\n-\nNatural killer\n- NSAID:\n-\nNon-steroidal anti-inflammatory drug\n- OXPHOS:\n-\nOxidative phosphorylation\n- PD-1:\n-\nProgrammed cell death protein-1\n- PDGF:\n-\nPlatelet-derived growth factor\n- PEV:\n-\nPlatelet-derived extracellular vesicle\n- PHGDH:\n-\nPhosphoglycerate dehydrogenase\n- PMP:\n-\nPlatelet-derived microparticle\n- PNP:\n-\nPlatelet-membrane-coated nanoparticle\n- ROS:\n-\nReactive oxygen species\n- SHMT:\n-\nSerine hydroxymethyltransferase\n- SSP:\n-\nSerine synthesis pathway\n- TCR:\n-\nT-cell receptor\n- TGF-β:\n-\nTransforming growth factor-beta\n- TIL:\n-\nTumor-infiltrating lymphocyte\n- TME:\n-\nTumor microenvironment\n- TPO:\n-\nThrombopoietin\n- TRAIL:\n-\nTNF-related apoptosis-inducing ligand\n- VEGF:\n-\nVascular endothelial growth factor\n- VWF:\n-\nVon Willebrand factor\nAcknowledgements\nNone.\nFunding\nNone.\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nEthics approval and consent to participate\nNot applicable.\nConsent for publication\nNot applicable.\nConsent to publish\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\nAbout this article\nCite this article\nHeydari, F., Zendehdel, H., Varkiani, M.M. et al. Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence. Biomark Res (2026). https://doi.org/10.1186/s40364-026-00957-5\nReceived:\nAccepted:\nPublished:\nDOI: https://doi.org/10.1186/s40364-026-00957-5","source_license":"public-domain-us","license_restricted":false}