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Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?
Mohammad Hossein Kazemi1,2, Maryam Sadri1,2, Alireza Najafi1,2
1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives.
Insights
Tumor-infiltrating lymphocytes (TILs) therapy shows promise for solid tumors by enhancing immune response. Despite challenges like cost and technical hurdles, TIL therapy offers a personalized approach for refractory cancers.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Tumor-infiltrating lymphocytes (TILs) are crucial for adaptive immunity against tumors but are often limited by low numbers and activity.
- The tumor microenvironment (TME) complexity has historically hindered TIL therapy success.
- Engineered T cells have advanced hematologic cancer immunotherapy, but solid tumor heterogeneity necessitates TILs with broad specificity.
Purpose of the Study:
- To review recent advancements in TIL therapy for solid tumors.
- To discuss the challenges and future perspectives of TIL-based immunotherapies.
- To highlight the potential of TIL therapy for patients with refractory solid tumors.
Main Methods:
- Review of recent literature on TIL therapy in solid tumors.
- Analysis of TME, immune exhaustion, and immune checkpoint roles in TIL efficacy.
- Examination of clinical trial data and outcomes for TIL therapy.
Main Results:
- TIL therapy is emerging as a safe, personalized immunotherapy with positive outcomes in metastatic melanoma, cervical, ovarian, and breast cancers.
- Recent understanding of TME and immune checkpoints has revitalized TIL therapy approaches.
- Several clinical trials are currently investigating TIL therapy efficacy in patients unresponsive to conventional treatments.
Conclusions:
- TIL therapy holds significant promise as a personalized immunotherapy for various solid tumors.
- Overcoming challenges such as cost, expansion time, and cell selection/activation is critical for widespread TIL therapy adoption.
- Continued research and clinical trials are essential to optimize TIL therapy and expand its application to a broader range of refractory cancers.
