“ TIL therapy has been applied successfully in patients with metastatic melanoma, breast cancer, ovarian cancer, cervical cancer, and other solid tumors, with favorable clinical outcomes reported in multiple studies. ”
BUFFALO, NY – August 31, 2026 – A new editorial was published in Volume 17 of Oncotarget on June 8, 2026, titled “ Tumor infiltrating lymphocyte (TIL) therapy for treating the solid tumors: Challenges and future perspectives .”
The editorial was led by first and corresponding author Bhartendra Sharma from Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan, India , along with co-authors Sukhbir Kaur, Vikas Sharma and Sanjay Soni.
Tumor-infiltrating lymphocyte (TIL) therapy is a form of adoptive cellular therapy that uses immune cells naturally present within tumors to attack cancer. Unlike chimeric antigen receptor (CAR) T-cell therapy, which genetically modifies a patient’s T cells to recognize specific tumor antigens and has achieved its greatest success in hematological malignancies, TIL therapy has shown potential in several types of solid tumors.
The approach has a history spanning more than four decades. Steven Rosenberg first isolated TILs from a mouse tumor in 1982, and subsequent experiments demonstrated antitumor effects when TILs were combined with cyclophosphamide and interleukin-2 (IL-2). In 1988, Rosenberg and colleagues reported favorable clinical outcomes after administering TIL therapy to patients with metastatic melanoma.
TIL therapy generally involves collecting naturally occurring lymphocytes from surgically obtained tumor tissue, expanding these cells outside the body, and reinfusing them into the patient. Before infusion, patients typically receive a non-myeloablative lymphodepletion regimen intended to suppress competing immune cells and improve the activity of the transferred TILs. High-dose IL-2 is then administered during treatment to support their survival, proliferation, and antitumor activity.
Despite encouraging clinical experience in metastatic melanoma and reports involving breast, ovarian, cervical, and other solid tumors, significant obstacles continue to limit broader use. Obtaining TILs generally requires surgical tumor tissue, which may be invasive and is not feasible for every patient. Even when tissue can be collected, obtaining sufficient material and isolating adequate numbers of tumor-reactive lymphocytes can remain challenging.
Another major barrier is the immunosuppressive tumor microenvironment. TILs can lose their ability to effectively eliminate cancer cells, while intratumor heterogeneity makes it difficult to develop approaches that work consistently across different patients and tumor types. The authors discuss combination strategies involving bispecific molecules, immune-checkpoint inhibitors, and local delivery of immune-stimulating therapies as potential ways to strengthen antitumor responses.
“ Additionally, the survival time of infused TIL is short-lived in vivo, highlighting the need for further improvements in TIL-therapies .”
Addressing T-cell exhaustion may also be important for improving treatment durability. The authors highlight advanced single-cell technologies, including single-cell RNA sequencing and single-cell mass cytometry, as tools for studying exhaustion markers and identifying TIL subsets with potentially stronger antitumor properties.
Future progress will therefore depend on improving methods for isolating and expanding highly tumor-reactive T cells while developing rational combination therapies that can overcome immune suppression and improve TIL persistence. These advances could help extend the benefits of TIL-based approaches across a broader range of solid tumors.
Overall, the editorial presents TIL therapy as a promising form of adoptive cellular immunotherapy for solid tumors while emphasizing the biological and practical barriers that still restrict its broader application. Continued research into T-cell selection, expansion, exhaustion, tumor heterogeneity, and combination treatments will be important for improving the effectiveness and durability of this therapeutic strategy.
DOI: https://doi.org/10.18632/oncotarget.28883
Correspondence to: Bhartendra Sharma – bhartendrasharma@mgumst.org
Intro video: https://www.youtube.com/watch?v=QAr_R4WCJfk
Keywords : cancer, tumor infiltrating lymphocytes, solid tumors, adoptive cellular therapy, immunotherapy
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Tumor infiltrating lymphocyte (TIL) therapy for treating the solid tumors: Challenges and future perspectives
8-Jun-2026
The authors have no conflicts of interest to declare.