Tumor-infiltrating lymphocytes: Prognostic considerations and current trials as adoptive cell therapy

Cancer remains one of the leading causes of mortality globally. In recent years, new treatments have been developed that capitalize on the patient’s own immune system to fight cancer including antibody-based immune checkpoint inhibition and adoptive cell therapy (ACT) using various cellular components of the immune system. Over the past few decades, it has been demonstrated that ACT using tumor-infiltrating lymphocytes (TIL) can successfully treat melanomas in patients for whom first and second line chemotherapies were not effective. Treatment of other solid tumors with TIL therapy has achieved durable cures in patients with advanced, metastatic disease; however, these outcomes are the exception and significant challenges remain. New advances in genetic engineering, particularly the use of CRISPR/Cas9 are currently being used to develop new TIL products to expand TIL-based ACT beyond melanoma treatment. In this review, we describe the history of ACT using TILs, TILs as a prognostic factor for cancer survival, new methods of improving TILs for ACT, and the current state of clinical research.