Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors?

Abstract

Lymphocytes in tumor tissue are called tumor-infiltrating lymphocytes (TILs), and they play a key role in the control and treatment of tumor diseases. Since the discovery in 1987 that cultured TILs can kill tumor cells more than 100 times more effectively than T-cells cultured from peripheral blood in melanoma, it has been confirmed that cultured TILs can successfully cure clinical patients with melanoma. Since 1989, after we investigated TIL isolation performance from solid tumors, we modified some procedures to increase efficacy, and thus successfully established new TIL isolation and culture methods in 1994. Moreover, our laboratory and clinicians using our cultured TILs have published more than 30 papers. To improve the efficacy of TILs, we have been carrying out studies of TIL efficacy to treat solid tumor diseases for approximately 30 years. The three main questions of TIL study have been “How do TILs remain silent in solid tumor tissue?”, “How do TILs attack homologous and heterologous antigens from tumor cells of solid tumors?”, and “How do TILs infiltrate solid tumor tissue from a distance into tumor sites to kill tumor cells?”. Research on these three issues has increasingly answered these questions. In this review I summarize the main issues surrounding TILs in treating solid tumors. This review aims to study the killing function of TILs from solid tumor tissues, thereby ultimately introducing the optimal strategy for patients suffering from solid tumors through personalized immunotherapy in the near future.