CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors - A narrative review

Sep 23, 2026

Uploaded by Mimi

Review examines how chimeric antigen receptor (CAR)-T cell therapy can be integrated with reconstructive oncologic surgery for peripheral solid tumors, including melanoma, sarcomas, breast cancer, and head and neck cancers. It explains why CAR-T efficacy in solid tumors remains constrained by tumor heterogeneity, immune suppression, and inadequate cellular infiltration. It summarizes emerging strategies such as localized CAR-T delivery, optimized CAR designs, and targeted antigen selection (HER2, MUC1, GD2, B7-H3). Discussed clinical findings suggest better local tumor control and potential benefits for surgical resection and reconstruction outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Summary

Background

Cancer burden and role of surgery

Peripheral solid tumors and reconstruction needs

CAR-T cells and the challenge in solid tumors

CAR design evolution and mechanisms

First- to fourth-generation CAR constructs

Cytokine release and immune modulation

Latest-generation design directions

ll OPEN ACCESS Review CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors—A narrative review Leonard Knoedler,1,2,3,* Konstantin Herfeld,4 Daniel A. Schaefer,5 Fortunay Diatta,1 James Clune,1 Brogan Evans,1 Michelle Seu,6 Bong-Sung Kim,7 Michael Alfertshofer,1 Thomas Schaschinger,1 Jasper Iske,8,9 Samuel Knoedler,1 Alexandre G. Lellouch,3 Maxime Jeljeli,3 Alberto Carturan,10,11 Marco Ruella,10,11 Max Heiland,2 Hendrik Poeck,4,12,13 Markus Perl,4,12 Bohdan Pomahac,1 and Martin Kauke-Navarro1,* 1Division of Plastic Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA 2Charit´e – Universit¨atsmedizin Berlin, Corporate Member of Freie Universit¨at Berlin, Humboldt-Universit¨at zu Berlin, and Berlin Institute of Health, Department of Oral and Maxillofacial Surgery, Berlin, Germany 3Division of Plastic and Reconstructive Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA 4Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany 5Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany 6Department of Neurology, Loyola University Medical Center, Maywood, IL, USA 7Department of Plastic Surgery and Hand Surgery, Zurich University Hospital, Zurich, Switzerland 8Department of Cardiothoracic Surgery, Deutsches Herzzentrum der Charit´e, Berlin, Germany 9Berlin Institute of Health at Charit´e – Universit¨atsmedizin Berlin, Berlin, Germany 10Center for Cellular Immunotherapies and Cellular Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA 11Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 12Bavarian Cancer Research Center (BZKF), Munich, Germany 13Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany *Correspondence: [leonard.knoedler@charite.de](leonard.knoedler@charite.de) (L. K.), [kauke-navarro.martin@yale.edu](kauke-navarro.martin@yale.edu) (M. K.-N.) [https://doi.org/10.1016/j.xcrm.2025.102240](https://doi.org/10.1016/j.xcrm.2025.102240) SUMMARY This review addresses the integration of chimeric antigen receptor (CAR)-T cell therapy with reconstructive oncologic surgery in treating peripheral solid tumors, including melanoma, sarcomas, breast cancer, and head and neck cancers. While CAR-T cells have demonstrated effectiveness in blood cancers, their efficacy in solid tumors has been limited due to tumor heterogeneity, immune suppression, and poor cellular infiltration. Emerging approaches involving localized CAR-T cell delivery, improved CAR design, and targeted antigen selection (such as HER2, MUC1, GD2, and B7-H3) are discussed as promising strategies to enhance therapeutic outcomes. Clinical studies highlighted in this review indicate improved local tumor control and potential to optimize surgical resections. Additionally, combining CAR-T therapy with surgery may reduce tumor recurrence and positively influence reconstructive outcomes. Overall, this review underscores CAR-T cell therapy as a potential adjunctive treatment in oncologic surgery, emphasizing the importance of interdisciplinary approaches to improve patient outcomes in solid tumor management. BACKGROUND Cancer continues to be the second most common cause of death in the US totaling 1.9 million new cases and 609,360 deaths in the US in 2022.1 About 60% of US cancer patients undergo surgical cancer treatment.2 Peripheral solid tumors (PSTs), such as breast, malignant skin, head and neck cancers, and sarcomas represent challenges for patients and providers.3 They commonly require primary resection, the therapeutic gold standard for localized stages.4–7 PST resection necessitates reconstructive surgery to support patient rehabilitation and improve postoperative quality of life.8–10 Current cancer guidelines suggest a close coordination of oncologic resect

FAQs

Why is CAR-T cell therapy less effective in peripheral solid tumors than in blood cancers?

Efficacy is limited by tumor heterogeneity, immune suppression, and poor CAR-T cellular infiltration into solid tumor tissue.

Which strategies does the review discuss to improve CAR-T performance in solid tumors?

It highlights localized CAR-T delivery, improved CAR engineering, and targeted antigen selection such as HER2, MUC1, GD2, and B7-H3.

How might combining CAR-T therapy with surgery affect treatment and reconstruction outcomes?

The review reports that combining therapy may enhance local tumor control, help optimize surgical resections, and potentially reduce recurrence while supporting reconstructive outcomes.

Sep 23, 2026

Uploaded by Mimi