Evidence map›Paper›PMID 41958653›Full record

ReviewFrontiers in immunology2026

Evolving therapeutic pipeline for tumor-infiltrating lymphocytes in metastatic melanoma - a review.

James Fan Wu, Muhammad Abbas Abid, Sharda P Singh, Virginia Mohlere, Muhammad Bilal Abid

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

James Fan WuDivision of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States.
Muhammad Abbas AbidDepartment of Pathology & Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Sharda P SinghTexas Tech University Health Science Center, UMC Cancer Center, Lubbock, TX, United States.
Virginia MohlereDepartment of Hematology/Oncology, The University of Texas Health Science Center at, Houston, TX, United States.
Muhammad Bilal AbidTexas Tech University Health Science Center, UMC Cancer Center, Lubbock, TX, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The recent U.S. FDA approval of lifileucel, a non-engineered, autologous tumor-infiltrating lymphocyte (TIL) therapy, for unresectable or metastatic melanoma represents a major milestone for cellular therapies in solid tumors. This review examines the clinical foundation, regulatory development, limitations, and evolution of TIL therapy in metastatic melanoma. Randomized academic data from the phase III M14TIL trial established the efficacy of TIL therapy. The C-144-01 study leading to lifileucel approval demonstrated median duration of response of 36.5 months, median overall survival (OS) of 13.9 months, and estimated 5-year OS rate of 19.7%, a major advance in this anti-PD-1/PD-L1 resistant cohort without effective treatment options. Despite durable responses, classical TIL therapy requires intensive nonmyeloablative lymphodepletion and high-dose interleukin-2 (IL-2), contributing to substantial toxicity and treatment-related mortality that remain barriers to broader implementation. We discuss safety-driven trial terminations related to cytokine augmentation and feasibility or strategic factors underlying discontinuation of programs, underscoring translational challenges beyond biologic efficacy. Engineered TIL platforms aim to improve persistence and reduce systemic cytokine dependence. OBX-115, designed with regulatable membrane-bound IL-15 expression, eliminates the need for IL-2 infusion and has shown early clinical activity. KSQ-001EX uses CRISPR/Cas9 to inactivate SOCS1, while KSQ-004EX additionally targets Regnase-1 to enhance TIL function. Emerging strategies including IL-2-independent expansion platforms, PD-1-edited TILs, and neoantigen-enriched products illustrate ongoing innovation. TIL therapy remains among the most promising strategies in melanoma and solid tumors after immunotherapy failure. Ongoing research aims to optimize cell dose, phenotype, tumor procurement, treatment sequencing, and rational combinations to improve durable benefit.

Indexed as

Immunotherapy, AdoptiveLymphocytes, Tumor-InfiltratingMelanomaAnimalsHumansNeoplasm Metastasisefficacymetastatic melanomasafetytumor-infiltrating lymphocytestumor microenvironment

Identifiers

PMID41958653
PMCPMC13057302

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.