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Review
. 2024 Mar 13;12(3):e008640.
doi: 10.1136/jitc-2023-008640.

Biomarkers for response to TIL therapy: a comprehensive review

Víctor Albarrán Fernández #  1   2 , Pablo Ballestín Martínez #  1   3 , Joachim Stoltenborg Granhøj  1 , Troels Holz Borch  1 , Marco Donia  1 , Inge Marie Svane  4
Affiliations
Review

Biomarkers for response to TIL therapy: a comprehensive review

Víctor Albarrán Fernández et al. J Immunother Cancer. .

Abstract

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2).

Keywords: Adoptive cell therapy - ACT; Biomarker; Immune Checkpoint Inhibitor; Solid tumor; Tumor infiltrating lymphocyte - TIL.

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Conflict of interest statement

Competing interests: JSG declares speakers’ fees from BMS. MD declares advisory fees from Achilles Therapeutics and proprietary data access for Bristol-Myers Squibb and Genentech. IMS declares honoraria for speaker, consultancy or advisory role for Roche, Novartis, MSD, BMS, TILT bio, Pierre Fabre, cofounder, stake/shareholder, and clinical advisor for IO Biotech. The CCIT-DK has received research grants from Adaptimmune, Lytix Biopharma, Enara Bio, TILT Biotherapeutics, Asgard Therapeutics, and BMS. The other authors declare no relevant competing interests.

Figures

Figure 1
Figure 1
Summarized representation of the potential patient-, tumor-, and treatment-related biomarkers for response to TIL therapy (in blue, purple, and green color, respectively). BRAF/MEKi, BRAF/MEK inhibitors; IL-2, interleukin-2; PD-1, programmed cell death protein 1; TIL, tumor-infiltrating lymphocyte.
See this image and copyright information in PMC

References

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