Melanoma clonal heterogeneity leads to secondary resistance after adoptive cell therapy with tumor-infiltrating lymphocytes
David König, Michael Sandholzer, Sarp Uzun, Andreas Zingg, Reto Ritschard, Helen Thut, Katharina Glatz, Elisabeth A. Kappos, Dirk J. Schaefer, Christoph Kettelhack, Jakob R. Passweg, Andreas Holbro, Katharina Baur, Michael Medinger, Andreas Buser, Didier Lardinois, Lukas T. Jeker, Nina Khanna, Frank Stenner, Benjamin Kasenda, Krisztian Homicsko, Matthias Matter, Natalia Rodrigues Mantuano, Alfred Zippelius, Heinz Läubli- Cancer Research
- Immunology
Abstract
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To our knowledge, this is the first case of clonal selection of a pre-existing non-dominant tumor cell clone and it demonstrates a mechanism involved in secondary resistance to TIL-ACT that could potentially change current clinical practice, because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before the treatment with TIL-ACT.