Pathological and Clinical Implications of Tumor Microenvironment Evaluated With Multiplex Immunohistochemistry in
Valentina Tateo1, Costantino Ricci2, Sofia Melotti2
1Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy.
Introduction:
Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Their development is closely linked to embryogenesis, yet much about their pathogenesis remains unknown. TGCTs exhibit exceptional sensitivity to cisplatin-based chemotherapy, achieving high cure rates even in metastatic disease. Further research is needed to deepen our understanding of TGCTs and refine risk stratification. In this pilot study, we focused on embryonal carcinoma (EC), a subtype with increased risk of relapse and considered a key step in TGCT reprogramming.
Patients And Methods:
We analyzed the tumor microenvironment (TME) in 49 EC samples using bright-field multiplex immunohistochemistry (BF-mIHC), which enables the simultaneous evaluation of multiple biomarkers, making it particularly useful for TME characterization. We evaluated B-cells (CD20), T-cells (CD3), and tumor-associated macrophages (TAMs, CD68) and established cutoffs that correlated with reprogramming phase, clinical stage, and relapse.
Results:
High TAM levels (CD68 + > 83/mm²) were strongly associated with phase I of reprogramming (pure EC or EC mixed only with seminoma), while low TAM characterized phase II (P<.001), suggesting a role in stemness maintenance through epigenetic regulation. High CD68 (> 46/mm²) and CD3 (> 125.5/mm²) correlated with metastatic disease (P<.001 and P=.026, respectively), whereas high CD20 (> 38.5/mm²) and CD3 (> 83/mm²) were linked to lower relapse risk (P=.014 and P=.017, respectively). Important limits are small sample size and few relapse events.
Conclusions:
These findings highlight the relevance of TME in TGCT biology and prognosis. The observed associations suggest TME may influence tumor plasticity, metastatization and relapse risk, warranting validation in larger studies.
Insights
Tumor microenvironment cells like macrophages and T-cells impact testicular germ cell tumor (TGCT) progression and relapse risk. Understanding these immune cells in embryonal carcinoma (EC) can improve TGCT treatment strategies.
Area of Science:
- Oncology
- Immunology
Background:
- Testicular germ cell tumors (TGCTs) are the most common cancer in young men, with pathogenesis linked to embryogenesis.
- TGCTs show high sensitivity to chemotherapy, but further understanding of TGCTs and risk stratification is needed.
- Embryonal carcinoma (EC) is a TGCT subtype with increased relapse risk, crucial for studying TGCT reprogramming.
Purpose of the Study:
- To analyze the tumor microenvironment (TME) in embryonal carcinoma (EC) samples.
- To investigate the correlation between immune cell populations and EC reprogramming, clinical stage, and relapse.
- To explore the prognostic significance of TME components in TGCT.
Main Methods:
- Analyzed 49 EC samples using bright-field multiplex immunohistochemistry (BF-mIHC).
- Evaluated B-cells (CD20), T-cells (CD3), and tumor-associated macrophages (TAMs, CD68).
- Established cutoffs for immune cell populations correlating with reprogramming phase, clinical stage, and relapse.
Main Results:
- High TAM (CD68) levels associated with early reprogramming phase (Phase I).
- High TAM (CD68) and T-cell (CD3) levels correlated with metastatic disease.
- High B-cell (CD20) and T-cell (CD3) levels linked to lower relapse risk.
Conclusions:
- The TME plays a significant role in TGCT biology and prognosis.
- TME components may influence tumor plasticity, metastasis, and relapse risk in TGCT.
- Findings suggest TME analysis could refine TGCT risk stratification and treatment strategies, requiring validation in larger cohorts.
