Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges

Abstract

Over the past decade, immunotherapy, especially cell-based immunotherapy, has provided new strategies for cancer therapy. Recent clinical studies demonstrated that adopting cell transfer of tumor-infiltrating lymphocytes (TILs) for advanced solid tumors showed good efficacy. TIL therapy is a type of cell-based immunotherapy using the patient’s own immune cells from the microenvironment of the solid tumor to kill tumor cells. In this review, we provide a comprehensive summary of the current strategies and challenges in TIL isolation and generation. Moreover, the current clinical experience of TIL therapy is summarized and discussed, with an emphasis on lymphodepletion regimen, the use of interleukin-2, and related toxicity. Furthermore, we highlight the clinical trials where TIL therapy is used independently and in combination with other types of therapy for solid cancers. Finally, the limitations, future potential, and directions of TIL therapy for solid tumor treatment are also discussed.

Neoantigens: promising targets for cancer therapy

“…379 Neoantigen-reactive TILs mediate a remarkable regression of epithelial cancers, including advanced breast cancer, metastatic cholangiocarcinoma, colorectal cancer, melanoma, and cervical cancers. 28,[380][381][382][383][384][385] In the earliest prospective study of neoantigenreactive T cells in epithelial cancers, metastatic cholangiocarcinoma patients with low TMB showed effective tumor regression lasting up to 35 months, offering the first concrete proof that neoantigen-targeted TILs can induce regression of metastatic epithelial cancer. Retrospective analysis of the infusion product has shown that the CD4 + T-helper 1 cells were reactive to an ERBB2IP mutation, suggesting a potential function of neoantigenspecific CD4 + T cells in the control of a metastatic epithelial cancer.…”

Current Landscape of Immunotherapy for Advanced Sarcoma

“…TIL therapy is based on the extraction of tumor-infiltrating lymphocytes for ex vivo expansion and reinfusion to the patient, after lymphodepleting conditioning, in combination with immune-enhancing adjuvants such as IL-2. It has an exciting potential, being the only ACT-using cells with multiple TCR clones able to cover the antigenic heterogeneity of solid tumors in contrast to engineered TCRs and CAR T cells, which target specific antigens [ 182 ]. Up to date, TIL therapy has been mainly developed in melanoma with a positive phase III trial versus ipilimumab in the first-line setting [ 183 ] and has promising results in cervical cancer [ 184 , 185 , 186 ], non-small cell lung cancer [ 187 ], ovarian cancer [ 188 ], colorectal cancer [ 189 ], breast cancer [ 190 ] and cholangiocarcinoma [ 191 ].…”

Prognostic value of neutrophil‐to‐lymphocyte ratio in patients with metastatic castration‐resistant prostate cancer receiving prostate‐specific membrane antigen targeted radionuclide therapy

“…34 Previously tested therapies with the intention of heating up the tumor microenvironment by activating this cell population are immunotherapy vaccines (e.g., PROSTVAC 36 ) and tumor-infiltrating lymphocyte therapy. 37 Similarly, radiation to all tumor sites can change the tumor microenvironment helping to prime and propagate antitumor immunity. 38 It may act as a cytotoxic and cause cell lysis and neoantigen release, 39 expose immunogenic mutations to the immune system, 40 and enhance the diversity of the T-cell receptor repertoire of intratumoral T cells.…”