Tumor-infiltrating lymphocytes for the treatment of metastatic cancer

• TIL therapy shows promising results for the treatment of cancer.
• Lymphodepletion prior to TIL depletes Tregs and removes cellular “sinks”.
• Preselection of TIL can lead to enrichment of tumor-reactive T cells.

Over the past few years melanoma incidence has been rising steadily, resulting in an increase in melanoma related mortality. Until recently, therapeutic options for metastatic melanoma were scarce. Chemotherapy and, in some countries, IL-2 were the only registered treatment modalities. In the last five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. Adoptive cell therapy using tumor-infiltrating lymphocytes is yet another, but highly promising, immunotherapeutic strategy for patients with metastatic melanoma. This review will discuss the development of TIL as a treatment option for melanoma, its mode of action and simplification over time, and the possibilities to expand this therapy to other types of cancer. Also, the future directions of TIL based therapies will be highlighted.