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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
PD-L1 expression in testicular germ cell tumors undergoing spontaneous regression
Ivan Novak1, Miroslav Tomić2, Denis Mulabdić3
1School of Medicine, University of Zagreb, Zagreb, Croatia.
Abstract:
Spontaneous regression of testicular germ cell tumors is a well-known phenomenon; however, the precise mechanisms of spontaneous regression are still unknown. Our study aimed to investigate programmed death-ligand 1 (PD-L1) expression in spontaneously regressed testicular germ cell tumors, exploring the link between the immune response and spontaneous regression. From a sample of 356 testicular germ cell tumors, we singled out 5 completely regressed and 6 partially regressed tumors. In four out of six cases with partial regression, a residual seminoma component was found, while in the remaining two cases, an embryonal carcinoma component was found. Comparisons were made with 20 pure seminomas and 20 mixed germ cell tumors (MGCTs). A semiquantitative immunohistochemical analysis of PD-L1 expression in tumor cells and intra/peritumoral lymphocytes was performed. There was no PD-L1 expression in tumors with complete regression. All partially regressed tumors showed expression in intra/peritumoral lymphocytes within the tumor remnants. Expression was significantly more frequent in pure seminomas compared to MGCTs (P = 0.004). A positive correlation was demonstrated between the seminoma component and the proportion of PD-L1 positive lymphocytes, with a Kendall's Tau-b coefficient of 0.626 (P < 0.001). Tumor cells showed PD-L1 expression in three MGCTs within the embryonal carcinoma component. Our results support an immunological mechanism of spontaneous tumor regression, with the strongest potential in testicular tumors containing seminoma components. However, further research is necessary to determine the role of PD-L1 ligand more precisely in the microenvironment of spontaneously regressed tumors.
Insights
Spontaneous regression of testicular tumors may involve immune responses. Programmed death-ligand 1 (PD-L1) expression was absent in completely regressed tumors but present in partially regressed ones, suggesting a role for PD-L1 in tumor regression.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Spontaneous regression of testicular germ cell tumors is observed but poorly understood.
- The underlying mechanisms driving tumor regression remain elusive.
- Investigating immune markers may elucidate spontaneous regression pathways.
Purpose of the Study:
- To examine programmed death-ligand 1 (PD-L1) expression in spontaneously regressed testicular germ cell tumors.
- To explore the association between PD-L1 expression and the immune response in tumor regression.
- To identify potential immunological mechanisms underlying spontaneous tumor regression.
Main Methods:
- Semiquantitative immunohistochemical analysis of PD-L1 expression in tumor cells and lymphocytes.
- Analysis of 5 completely regressed, 6 partially regressed, 20 pure seminomas, and 20 mixed germ cell tumors (MGCTs).
- Correlation analysis between PD-L1 expression, tumor components (seminoma, embryonal carcinoma), and lymphocyte infiltration.
Main Results:
- No PD-L1 expression was detected in completely regressed tumors.
- Partially regressed tumors exhibited PD-L1 expression in intra/peritumoral lymphocytes.
- PD-L1 expression was more frequent in pure seminomas than MGCTs, with a positive correlation between seminoma component and PD-L1 positive lymphocytes.
Conclusions:
- Results suggest an immunological basis for spontaneous testicular tumor regression.
- The seminoma component appears to be associated with a stronger immune response indicated by PD-L1 expression.
- Further research is needed to clarify the precise role of PD-L1 in the tumor microenvironment during spontaneous regression.
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