Case Report: Durable response to tumor-infiltrating lymphocyte therapy in a patient with metastatic melanoma and chronic lymphocytic leukemia/small lymphocytic lymphoma
Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy for the treatment of immune checkpoint therapy-resistant/refractory advanced melanoma patients. However, its safety and efficacy remain to be determined among patients with concurrent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and advanced melanoma. This case is the first to demonstrate the successful treatment of a metastatic melanoma patient with concurrent CLL/SLL using lymphodepleting chemotherapy followed by unselected TIL and interleukin-2. The treatment was safe with no new toxicities observed, resulting in a durable radiological partial response and molecular response with the complete clearance of detectable circulating tumor DNA. The microenvironment of the harvested melanoma used to generate the TIL product contained an abundance of CD8<sup>+</sup>TCF1<sup>+</sup> and CD8<sup>+</sup>CD69<sup>+</sup> T cells, spatial co-clustering of CD8<sup>+</sup> T cells with CD11c myeloid networks. Despite containing SLL deposits, the harvested melanoma produced a CD8<sup>+</sup> T cell-predominant tumor-reactive TIL infusion product containing stem-like CD39<sup>neg</sup>CD69<sup>neg</sup> CD8<sup>+</sup> T cells. A strong overlap (60%) in the TCRβ sequences between this infusion product and peripheral blood mononuclear cells collected at the 9-month follow-up visit was evidence of long-term persistence of TIL in this patient.
Authors
- MacLean Hall (ORCID: https://orcid.org/0000-0002-5626-1619)
- James J. Mulé (ORCID: https://orcid.org/0000-0001-7354-0516)
- Shari Pilon‐Thomas (ORCID: https://orcid.org/0000-0001-7785-3034)
- Zeynep Eroglu
- Carlos Moran Segura (ORCID: https://orcid.org/0000-0001-8702-0554)
- Jane L. Messina (ORCID: https://orcid.org/0000-0002-0332-0224)
- Jinming Song (ORCID: https://orcid.org/0000-0001-5642-1451)
- Frederick Lundry Locke (ORCID: https://orcid.org/0000-0001-9063-6691)
- Douglas Buckner Johnson (ORCID: https://orcid.org/0000-0002-6390-773X)
- Johannes Ali
- Amod A. Sarnaik (ORCID: https://orcid.org/0000-0002-2337-5898)
- Matthew Perez (ORCID: https://orcid.org/0009-0005-5348-3020)
- Kenneth Yee Tsai (ORCID: https://orcid.org/0000-0001-5325-212X)
- John E. Mullinax (ORCID: https://orcid.org/0000-0002-9596-6785)
- Elizabeth DiMaggio (ORCID: https://orcid.org/0000-0002-8745-7753)
- Nikhil I. Khushalani (ORCID: https://orcid.org/0000-0002-3636-4143)
- Hanna Bailey (ORCID: https://orcid.org/0009-0005-9959-7162)
- David Morgan (ORCID: https://orcid.org/0000-0002-6959-5079)
- Denise Kalos (ORCID: https://orcid.org/0009-0008-0576-3222)
- Matthew S. Beatty (ORCID: https://orcid.org/0000-0001-5734-1322)
- Lilit Karapetyan (ORCID: https://orcid.org/0000-0001-8530-0907)
- Jin Xu (ORCID: https://orcid.org/0000-0002-4964-9404)
- Javier Pinilla‐Ibarz (ORCID: https://orcid.org/0000-0003-3170-9648)
- Eliane Vieira (ORCID: https://orcid.org/0000-0001-8610-4924)
- Peiling Chen (ORCID: https://orcid.org/0000-0003-0636-3032)
- Joel Kuriakose
- Karla E. Adams (ORCID: https://orcid.org/0009-0005-0010-8323)
- Vernon K. Sondak
- Christopher D. Otteni
- Lianicet Rodriguez-Alfonso
Institutions
- University of South Florida (US)
- Moffitt Cancer Center (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-11-17
- DOI
- https://doi.org/10.3389/fimmu.2025.1718443
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation