Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer

// Hee Jin Lee 1, * , Young-Ae Kim 1, 2, * , Chan Kyu Sim 3, * , Sun-Hee Heo 1, 2 , In Hye Song 1 , Hye Seon Park 1, 2 , Suk Young Park 1, 2 , Won Seon Bang 1, 2 , In Ah Park 1 , Miseon Lee 1 , Jung Hoon Lee 3 , Yeon Sook Cho 3 , Suhwan Chang 4 , Jaeyun Jung 4 , Jisun Kim 5 , Sae Byul Lee 5 , Sung Youl Kim 6 , Myeong Sup Lee 3, # and Gyungyub Gong 5, # 1 Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 2 Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 3 Lab of Molecular Immunology and Medicine, Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea 4 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea 5 Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 6 RD tumor-infiltrating lymphocyte; adoptive cell transfer; memory T cell; function of TIL Received: July 12, 2017      Accepted: November 13, 2017      Published: December 06, 2017 ABSTRACT Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro . Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.