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- Titel:
The immune checkpoint LAG-3 is expressed by melanoma cells and correlates with clinical progression of the melanoma.
- Dokumenttyp:
- Journal Article
- Autor(en):
- Wiecken, Melanie; Machiraju, Devayani; Chakraborty, Shounak; Mayr, Eva-Maria; Lenoir, Bénédicte; Eurich, Rosa; Richter, Jasmin; Pfarr, Nicole; Halama, Niels; Hassel, Jessica C
- Abstract:
- Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome. LAG-3 and TIM-3 were commonly expressed in melanoma cells. In the stage IV cohort, expression of LAG-3 was associated with M1 stage (p < 0.001) and previous exposure to immune checkpoint inhibitors (p = 0.029). Moreover, in the anti-PD-1 monotherapy treatment group patients with high LAG-3 expression by tumor cells tended to have a shorter progression-free survival (p = 0.088), whereas high expression of TIM-3 was associated with a significantly longer overall survival (p = 0.007). In conclusion, we provide a systematic analysis of melanoma cell intrinsic LAG-3 and TIM-3 expression, highlighting potential implications of their expression on patient survival.
- Zeitschriftentitel:
- Oncoimmunology
- Jahr:
- 2025
- Band / Volume:
- 14
- Heft / Issue:
- 1
- Volltext / DOI:
- doi:10.1080/2162402X.2024.2430066
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/39716918
- Print-ISSN:
- 2162-4011
- TUM Einrichtung:
- Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.)
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