Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells.

Autor: Tran TT; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Rane CK; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Zito CR; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA.; Department of Biology, School of Arts, Sciences, Business, and Education, University of Saint Joseph, West Hartford, CT 06117, USA., Weiss SA; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Jessel S; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Lucca L; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA., Lu BY; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA.; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA., Oria VO; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Adeniran A; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA., Chiang VL; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA., Omay SB; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA., Hafler DA; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA., Kluger HM; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA., Jilaveanu LB; Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Mar 02; Vol. 13 (5). Date of Electronic Publication: 2021 Mar 02.
DOI: 10.3390/cancers13051049
Abstrakt: Little is known about the subcellular localization and function of programmed cell death 4 (PDCD4) in melanoma. Our past studies suggest PDCD4 interacts with Pleckstrin Homology Domain Containing A5 (PLEKHA5) to influence melanoma brain metastasis outcomes, as high intracranial PDCD4 expression leads to improved survival. We aimed to define the subcellular distribution of PDCD4 in melanoma and in the tumor microenvironment during neoplastic progression and its impact on clinical outcomes. We analyzed multiple tissue microarrays with well-annotated clinicopathological variables using quantitative immunofluorescence and evaluated single-cell RNA-sequencing on a brain metastasis sample to characterize PDCD4+ immune cell subsets. We demonstrate differences in PDCD4 expression during neoplastic progression, with high tumor and stromal PDCD4 levels associated with improved survival in primary melanomas and in intracranial metastases, but not in extracranial metastatic disease. While the expression of PDCD4 is well-documented on CD8+ T cells and natural killer cells, we show that it is also found on B cells and mast cells. PDCD4 expression in the tumor microenvironment is associated with increased immune cell infiltration. Further studies are needed to define the interaction of PDCD4 and PLEKHA5 and to evaluate the utility of this pathway as a therapeutic target in melanoma brain metastasis.
Databáze: MEDLINE
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