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Immune-Proteome Profiling in Classical Hodgkin Lymphoma Tumor Diagnostic Tissue
Alex Reza Gholiha1, Peter Hollander2, Liza Löf3
1Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, SE-752 36 Uppsala, Sweden.
Insights
This study identified distinct immune protein profiles in classical Hodgkin Lymphoma (cHL) tissues and plasma. These findings reveal potential biomarkers for cHL diagnosis and understanding its immune evasion mechanisms.
Area of Science:
- Immunology
- Oncology
- Proteomics
Background:
- Classical Hodgkin Lymphoma (cHL) utilizes immunoediting through protein signaling to evade immune surveillance.
- Identifying immune-related proteins is crucial for understanding cHL pathogenesis and developing diagnostic tools.
Purpose of the Study:
- To identify immune-related proteins that differentiate diagnostic cHL tissues from control tissues.
- To correlate these tissue findings with the plasma proteome profile in cHL patients versus healthy controls.
Main Methods:
- Proximity extension assay (PEA) using the OlinkTM multiplex Immuno-Oncology panel (92 proteins).
- Analysis of diagnostic cHL tissues (n=27) and reactive lymph node tissues (n=30).
- Comparison of plasma proteomes between cHL patients (n=26) and healthy controls (n=27).
- Statistical analysis including univariate, multivariate-adjusted analysis, and Benjamini-Hochberg's false discovery rate (Padj).
Main Results:
- More proteins distinguished cHL cases in plasma (30 proteins) than in tissue (17 proteins), all with Padj < 0.05.
- Eight proteins (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, LAG3) were elevated in both cHL tissues and plasma compared to controls.
- Six proteins in cHL tissue correlated significantly with PD-L1 expression (IL-6, MCP-2, CCL3, CCL4, GZMB, IFN-gamma).
Conclusions:
- This study establishes a distinct proteomic profile for cHL tissue.
- Identified immune-related proteins serve as potential biomarkers for cHL pathophysiology and immune evasion.
Abstract:
In classical Hodgkin Lymphoma (cHL), immunoediting via protein signaling is key to evading tumor surveillance. We aimed to identify immune-related proteins that distinguish diagnostic cHL tissues (=diagnostic tumor lysates, n = 27) from control tissues (reactive lymph node lysates, n = 30). Further, we correlated our findings with the proteome plasma profile between cHL patients (n = 26) and healthy controls (n = 27). We used the proximity extension assay (PEA) with the OlinkTM multiplex Immuno-Oncology panel, consisting of 92 proteins. Univariate, multivariate-adjusted analysis and Benjamini-Hochberg's false discovery testing (=Padj) were performed to detect significant discrepancies. Proteins distinguishing cHL cases from controls were more numerous in plasma (30 proteins) than tissue (17 proteins), all Padj < 0.05. Eight of the identified proteins in cHL tissue (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, and LAG3) were elevated in both cHL tissues and cHL plasma compared with control samples. Six proteins distinguishing cHL tissues from controls tissues were significantly correlated to PD-L1 expression in cHL tissue (IL-6, MCP-2, CCL3, CCL4, GZMB, and IFN-gamma, all p ≤0.05). In conclusion, this study introduces a distinguishing proteomic profile in cHL tissue and potential immune-related markers of pathophysiological relevance.
