Related Experiment Video
Updated: Nov 10, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells
Thuy T Tran1, Chetan K Rane1, Christopher R Zito1,2
1Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT 06510, USA.
Abstract:
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.
Insights
Programmed cell death 4 (PDCD4) in melanoma is linked to better survival, especially in brain metastases. High PDCD4 levels in tumors and the surrounding immune cells correlate with improved patient outcomes.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Programmed cell death 4 (PDCD4) function and localization in melanoma remain largely uncharacterized.
- Previous research indicates PDCD4's interaction with PLEKHA5 influences melanoma brain metastasis, with higher PDCD4 correlating with better survival in intracranial disease.
Purpose of the Study:
- To determine the subcellular distribution of PDCD4 in melanoma.
- To investigate PDCD4's role in the tumor microenvironment during melanoma progression.
- To assess the impact of PDCD4 expression on clinical outcomes in melanoma patients.
Main Methods:
- Quantitative immunofluorescence on tissue microarrays with clinical data.
- Single-cell RNA-sequencing of a brain metastasis sample.
- Analysis of PDCD4 expression in tumor cells and immune subsets.
Main Results:
- PDCD4 expression varies during melanoma progression.
- Elevated tumor and stromal PDCD4 levels are associated with improved survival in primary and intracranial metastatic melanomas.
- PDCD4 is expressed on B cells and mast cells, in addition to CD8+ T and NK cells.
- Increased PDCD4 expression in the tumor microenvironment correlates with enhanced immune cell infiltration.
Conclusions:
- PDCD4 expression patterns and localization provide prognostic value in melanoma, particularly for brain metastases.
- PDCD4 is present on a broader range of immune cells than previously known.
- Further research into the PDCD4-PLEKHA5 pathway may reveal therapeutic targets for melanoma brain metastasis.
More Related Videos
06:16Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
08:30Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
