Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer
Abstract
:1. Introduction
2. Material and Methods
2.1. Prostate Cancer Tissue Samples
2.2. Cell Culture and Chemicals
2.3. Drugs and Antibodies
2.4. Construction and Transfection of Plasmids Expressing AIM/CD5L
2.5. Cell Viability and Proliferation Colorimetric Assay
2.6. Immunohistochemical (IHC) Staining Assays
2.7. Scratch Wound-Healing Migration Assay
2.8. Invasion Assay
2.9. Public Cancer Dataset Access and Analysis
2.10. Statistical Analysis
3. Results
3.1. AIM and PSA Expression Levels Are Inversely Correlated in Patients with Prostate Cancer
3.2. Aberrantly Expressed PSA and Significantly Suppressed AIM Expression Characterize Advanced Stage Prostate Cancer, Regardless of Mutation Status
3.3. The Differential Expression of PSA and AIM Is Associated with Disease Recurrence in Patients with Prostate Cancer but Is Equivocal for Overall Survival
3.4. PSA-Associated Suppression of AIM Is Implicated in the Enhanced Metastability of Prostate Cancer and a High AIM/PSA Ratio Is Associated with Strong Castration-Induced Regression
3.5. The Functional Association between PSA and AIM Modulates Metastasis and Mirrors the Immunogenicity in Patients with Prostate Cancer
3.6. The Inversely Correlated Expression of PSA and AIM Differentially Modulate Treg, T cell, and Macrophage Activities in Patients with Prostate Cancer
3.7. AIM Binds Directly to PSA, and the AIM-PSA Interactome Reveals Complicity in Immune Landscape, Macrophage, EMT and CSC Regulation
3.8. Ectopic (Re)Expression of AIM Enhances the Anticancer Therapeutic Effect of Pembrolizumab against PCa Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
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Bamodu, O.A.; Wang, Y.-H.; Yeh, C.-T.; Ho, C.-H.; Chiang, Y.-T.; Kao, W.-T.; Liu, C.-H.; Wu, C.-C. Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer. Biomedicines 2021, 9, 1225. https://doi.org/10.3390/biomedicines9091225
Bamodu OA, Wang Y-H, Yeh C-T, Ho C-H, Chiang Y-T, Kao W-T, Liu C-H, Wu C-C. Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer. Biomedicines. 2021; 9(9):1225. https://doi.org/10.3390/biomedicines9091225
Chicago/Turabian StyleBamodu, Oluwaseun Adebayo, Yuan-Hung Wang, Chi-Tai Yeh, Chen-Hsun Ho, Yi-Te Chiang, Wei-Tang Kao, Chia-Hung Liu, and Chia-Chang Wu. 2021. "Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer" Biomedicines 9, no. 9: 1225. https://doi.org/10.3390/biomedicines9091225
APA StyleBamodu, O. A., Wang, Y.-H., Yeh, C.-T., Ho, C.-H., Chiang, Y.-T., Kao, W.-T., Liu, C.-H., & Wu, C.-C. (2021). Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer. Biomedicines, 9(9), 1225. https://doi.org/10.3390/biomedicines9091225