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Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and
Niki Gavrielatou1, Ioannis Vathiotis1, Thazin Nwe Aung1
1Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
Abstract:
Programmed cell death protein-1 (PD-1)-targeted immunotherapy is approved for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Although its efficacy correlates with PD-L1 expression, response is limited even among positive cases. We employed digital spatial profiling (DSP) to discover potential biomarkers of immunotherapy outcomes in HNSCC. Fifty prospectively collected, pretreatment biopsy samples from patients with anti-PD-1-treated R/M HNSCC, were assessed using DSP, for 71 proteins in four molecularly defined compartments (tumor, leukocyte, macrophage, and stroma). Markers were evaluated for associations with progression-free (PFS) and overall survival (OS). High beta-2 microglobulin (B2M), LAG-3, CD25, and 4-1BB in tumor; high B2M, CD45, CD4 in stroma, and low fibronectin in the macrophage compartment, correlated with prolonged PFS. Improved PFS and OS were observed for cases with high B2M by quantitative and mRNA. Findings were validated in an independent cohort for PFS (HR, 0.41; 95% confidence interval, 0.19-0.93; P = 0.034). B2M-high tumors showed enrichment with immune cell and immune checkpoint markers. Our study illustrates B2M expression is associated with improved survival for immune checkpoint inhibitor (ICI)-treated HNSCC.
Significance:
In the current study, DSP revealed the positive association of B2M expression in the tumor compartment with immunotherapy outcomes in R/M HNSCC.
Insights
High beta-2 microglobulin (B2M) expression in tumors is linked to better survival for patients with recurrent or metastatic head and neck squamous cell carcinoma receiving immunotherapy. This biomarker discovery aids in predicting treatment response.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Programmed cell death protein-1 (PD-1) immunotherapy is approved for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
- Treatment efficacy is limited, even in PD-L1 positive cases, necessitating novel biomarker identification.
Purpose of the Study:
- To identify potential biomarkers predicting immunotherapy outcomes in R/M HNSCC using digital spatial profiling (DSP).
- To evaluate associations between protein expression and progression-free survival (PFS) and overall survival (OS).
Main Methods:
- DSP was used to analyze 71 proteins across tumor, leukocyte, macrophage, and stroma compartments in 50 R/M HNSCC biopsy samples.
- Associations between protein markers and PFS/OS were assessed.
- Key findings were validated in an independent cohort.
Main Results:
- High beta-2 microglobulin (B2M) expression in the tumor compartment correlated with prolonged PFS and improved OS.
- Other markers like LAG-3, CD25, and 4-1BB in the tumor, and CD45, CD4 in stroma were also associated with PFS.
- B2M-high tumors showed enrichment of immune cell and immune checkpoint markers.
Conclusions:
- Beta-2 microglobulin (B2M) is a promising biomarker associated with improved survival in R/M HNSCC patients treated with immune checkpoint inhibitors (ICIs).
- DSP is a valuable tool for discovering biomarkers of ICI response in HNSCC.
