CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Durable response to tumor-infiltrating lymphocyte therapy in a patient with metastatic melanoma and chronic lymphocytic leukemia/small lymphocytic lymphoma
Provisionally accepted
Lilit Karapetyan1*
Joel Kuriakose1
Matthew Perez1Johannes Ali1
MacLean Hall1
Matthew S Beatty1Christopher Otteni1Jin Xu2
Denise Kalos2Carlos Moran-Segura1Ella Vieira1Karla Adams1Lianicet Rodriguez-Alfonso1Elizabeth C DiMaggio1Hanna Bailey1
Javier Pinilla-Ibarz1Frederick Locke1
John Mullinax1Pei-Ling Chen1
Jinming Song1
Jane L Messina1
Douglas Johnson3
David Morgan3
Zeynep Eroglu1
Nikhil I Khushalani1
Vernon Sondak1
Amod Ashok Sarnaik1
Kenneth Y Tsai1
James Joseph Mule'1
Shari Pilon-Thomas1- 1Moffitt Cancer Center, Tampa, United States
- 2Moffitt Cancer Center Department of Biostatistics and Bioinformatics, Tampa, United States
- 3Vanderbilt University Medical Center, Nashville, United States
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Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy for the treatment of immune checkpoint therapy resistant/refractory advanced melanoma patients. However, 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 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 complete clearance of detectable circulating tumor DNA. The microenvironment of the harvested melanoma used to generate the TIL product contained an abundance of CD8+TCF1+ and CD8+CD69+ T cells, spatial co-clustering of CD8+ T cells with CD11c myeloid networks. Despite containing SLL deposits, the harvested melanoma produced a CD8+ T cell predominant tumor-reactive TIL infusion product containing stem-like CD39negCD69neg CD8+ T cells. A strong overlap (60%) in the TCR sequences between this infusion product and peripheral blood mononuclear cells collected at 9-month follow up visit was evidence of long-term persistence of TIL in this patient.
Keywords: Melanoma, tumor infiltrating lymphocytes, Chronic lymphocytic leukemia/small lymphocytic lymphoma, cell therapy, Adoptive cell immunotherapy
Received: 03 Oct 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Karapetyan, Kuriakose, Perez, Ali, Hall, Beatty, Otteni, Xu, Kalos, Moran-Segura, Vieira, Adams, Rodriguez-Alfonso, DiMaggio, Bailey, Pinilla-Ibarz, Locke, Mullinax, Chen, Song, Messina, Johnson, Morgan, Eroglu, Khushalani, Sondak, Sarnaik, Tsai, Mule' and Pilon-Thomas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lilit Karapetyan, lilit.karapetyan@moffitt.org
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.