Penile cancer is a rare but highly lethal cancer, and therapeutic options for patients presenting with lymph nodal disease are very limited. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) was shown to provide durable objective response in patients with metastatic melanoma and TIL have been expanded from solid tumors at rates between 70 and 90% depending on the specific diagnosis. We evaluated whether TIL could be expanded from surgical specimens of patients with penile cancer. Tumor samples from metastatic lymph nodes obtained at the time of inguinal lymph node dissection were collected, minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. The phenotype of expanded TILs was assessed by flow cytometry and their anti-tumor reactivity was assessed by IFN-γ ELISA. TIL were expanded from 11 out of 12 (91.6%) samples of metastatic lymph nodes. Expanded TIL were predominantly CD3+ (mean 67.5%, SD 19.4%) with a mean of 46.8% CD8+ T cells (SD 21.1%). Five out of 11 samples (45.4%) from expanded TIL secreted IFN-γ in response to autologous tumor. TIL expansion and phenotype of expanded T cell lymphocytes were independent of previous HPV infection and treatment with neoadjuvant chemotherapy. This is the first report demonstrating successful expansion of tumor-reactive TIL from penile cancer patients, which support development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.
International immunopharmacology. 2021 Feb 23 [Epub ahead of print]
Ahmet Murat Aydin, MacLean Hall, Brittany L Bunch, Holly Branthoover, Zachary Sannasardo, Amy Mackay, Matthew Beatty, Amod A Sarnaik, John E Mullinax, Philippe E Spiess, Shari Pilon-Thomas
Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA., Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA; Cancer Biology PhD Program, University of South Florida, Tampa, FL, USA., Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA., Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA; Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA., Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA; Sarcoma Program, Moffitt Cancer Center, Tampa, FL, USA., Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA; Center for Immunization and Infection Research in Cancer (CIIRC), Moffitt Cancer Center, Tampa, FL, USA. Electronic address: .