Luke V. Selby, MD MS FACS FSSO
Assistant Professor of Surgery
University of Kansas Medical Center
Leawood, Kansas, United States
Jordan Baker, MS
Department of Biostatistics & Data Science, University of Kansas Medical Center
Kansas City, Kansas, United States
Prabhakar Chalise, PhD
Associate Professor
Department of Biostatistics & Data Science, University of Kansas Medical Center
Kansas City, Kansas, United States
Matthew C. Perez, MD
Surgical Oncologist, Department of Cutaneous Oncology
Moffitt Cancer Center
Tampa, Florida, United States
Martin D. McCarter, MD
Professor of Surgery
Department of Surgery, University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
David Moskal, MD
Surgery Resident
Department of Surgery, University of Colorado Anschutz Medical Campus
Denver, Colorado, United States
Kelly Olino, MD (she/her/hers)
Assistant Professor
Department of Surgery, Yale University
New Haven, Connecticut, United States
Gabriela R. Esnaola, BA
Department of Surgery, Yale University
New Haven, Connecticut, United States
Jeffrey E. Johnson, M.D.
Assistant Professor of Surgery
Department of Surgery, Mayo Clinic
Rochester, Minnesota, United States
Jessica Crystal, MD
Surgical Oncologist
Department of Surgery, University of Miami Miller School of Medicine
Miami, Florida, United States
Ashley M. Holder, MD (she/her/hers)
Associate Professor of Surgical Oncology
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Alexandra C. Istl, MD, MPH, FRCSC, FSSO (she/her/hers)
Assistant Professor
(1) Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin and 2) MCW Cancer Center,
Milwaukee, Wisconsin, United States
Edmund Bartlett, M.D., PhD
Co-author
Memorial Sloan Kettering
New York, New York, United States
Sonia Cohen, MD, PhD (she/her/hers)
Assistant Professor of Surgery
Massachusetts General Hospital
Boston, Massachusetts, United States
Joal D. Beane, MD
Assistant Professor
Department of Surgery, The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Myles J. Smith, MB BCh BAO, PhD, FRCSI, FRCS
Consultant Surgical Oncologist and General Surgeon,
Department of Surgery, The Royal Marsden Hospital and Institute of Cancer Research
London, England, United Kingdom
Amanda R. Kirane, MD PhD (she/her/hers)
Assistant Professor
Stanford University
Palo Alto, California, United States
Sarah B. Bateni, MD
Assistant Professor
University of Alabama at Birmingham
Vestavia Hills, Alabama, United States
Cristina O'Donoghue, MD, MPH (she/her/hers)
Surgical Oncologist
University of Chicago Pritzker School of Medicine
Chicago, California, United States
Julia Terhune, MD
Assistant Professor
Department of Surgery, University of Maryland
Baltimore, Maryland, United States
Giorgos C. Karakousis, MD (he/him/his)
Professor of Surgery
Department of Surgery, University of Pennsylvania Health System, United States
Amanda Dann, MD
Assistant Professor
Department of Surgery, UT Southwestern
Dallas, Texas, United States
Winan J. van Houdt, MD
Surgical oncologist
Department of Surgery, Netherland Cancer Institute
Amsterdam, Noord-Holland, Netherlands
John E. Mullinax, MD
Associate Member; Section head Surgical Oncology Sarcoma Department
Moffitt Cancer Center
Tampa, Florida, United States
Aubrey C. Swilling, DO, MS
Resident Physician
Department of Surgery, University of Kansas Medical Center
Kansas City, Missouri, United States
Autologous tumor infiltrating lymphocyte (TIL) cell therapy is a treatment for patients with metastatic melanoma who have progressed on systemic therapy. TIL therapy requires surgical tumor tissue procurement (TTP) for product manufacturing, including TIL isolation, expansion, and infusion. Data is limited on how surgical factors impact TIL manufacturing success; the current standard is to select a site that will result in at least 1.5cm2 of viable tissue. FDA specifications for TIL products are largely undisclosed other than the final product contains 7.5 - 72x109 cells. The aim of the TIL TTP Working Group, a multi-institutional collaborative, is to optimize TTP. The aim of this study is to identify predictors of initial manufacturing success to guide future TTP site selection.
Methods:
Patients who underwent TTP at a TIL TTP Working Group center with available manufacturing outcomes were included after local IRB approval. Clinical, oncologic, peri-operative, and outcome variables were collected. The primary outcome was initial manufacturing success, defined as production of an in-spec TIL product. Secondary outcomes were variables associated with manufacturing success.
Results:
Between December 2023 and August 2025, 87 patients from six institutions underwent TTP for commercial TIL, 85% (74/87) of which resulted in manufacturing success. Aggregate size (cm2), history of immunosuppression or being on steroids at the time of TTP, donor tissue type, or preoperative Hounsfield units were not associated with manufacturing success. Four of the six patients who received radiation to the TTP donor site had successfully manufactured TIL (p=0.22). Although not statistically significant, higher SUV on pre-operative PET may be associated with a decreased likelihood of manufacturing success with a larger cohort (mean[SD] success: 16.09[14.60] vs 28.68[22.04], p =0.09). Necrosis on final pathology was not associated with a decreased likelihood of manufacturing success, though was not reported in 34.5% of patients. However, surgeon assessment of gross necrosis during TTP was associated with a decreased likelihood of manufacturing success (in-spec: 9%, out-of-spec: 33.3%, p=0.04).
Conclusions:
The TIL TTP Working Group was established to optimize TIL TTP in the real-world setting. In this initial series, gross necrosis during TTP was associated with a decreased likelihood of manufacturing success, and elevated SUV of the donor site on PET warrants further investigation. Multi-institutional and academic-industry partnerships are essential to improve TIL TTP outcomes.