Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions


INTRODUCTION: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a highly personalized type of cancer immunotherapy. TIL-based ACT exploits naturally occurring TILs, derived from the patients' tumor. This treatment has shown consistent clinical responses in melanoma, and recent results point toward a potential use in multiple cancer diagnoses. However, several limitations have restricted the clinical development and adaptation of TIL-based ACT.

AREAS COVERED: In this review, we present the principles of TIL-based ACT and discuss the most significant limitations for therapeutic efficacy and its widespread application. The topics of therapeutic resistance (both innate and acquired), treatment-related toxicity, and the novel research topic of metabolic barriers in the tumor microenvironment (TME) are covered.

EXPERT OPINION: There are many ongoing areas of research focusing on improving clinical efficacy and optimizing TIL-based ACT. Many strategies have shown a great potential, particularly strategies advancing TIL efficacy (such as increasing and harnessing ex vivo the sub-population of tumor-reactive TILs) and manufacturing processes. Novel approaches can help overcome current limitations and potentially result in TIL-based ACT entering the mainstream of cancer therapy across tumor types.

Original languageEnglish
JournalExpert Opinion on Biological Therapy
Issue number5
Pages (from-to)627-641
Number of pages15
Publication statusPublished - May 2022


  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive/methods
  • Lymphocytes, Tumor-Infiltrating
  • Melanoma/pathology
  • Tumor Microenvironment


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