Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma.
Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.1158/2767-9764.crc-22-0299
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发表时间：
2023-04
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程序性细胞死亡蛋白-1（PD-1）靶向免疫疗法被批准用于复发性或转移性头颈部鳞状细胞癌（R/M HNSCC）治疗。尽管其疗效与PD-L1表达相关，但即使在阳性病例中，反应也有限。我们采用数字空间分析（DSP）来发现HNSCC免疫治疗结果的潜在生物标志物。使用DSP评估了从抗PD-1治疗的R/M HNSCC患者中前瞻性收集的50份治疗前活检样本的4个分子定义区室（肿瘤、白细胞、巨噬细胞和基质）中的71种蛋白质。评估标志物与无进展（PFS）和总生存期（OS）的相关性。肿瘤中的高β 2微球蛋白（B2 M）、LAG-3、CD 25和4-1BB;基质中的高B2 M、CD 45、CD 4和巨噬细胞室中的低纤连蛋白与PFS延长相关。通过定量和mRNA检测，观察到高B2 M病例的PFS和OS改善。在独立队列中验证了PFS结果（HR，0.41; 95%置信区间，0.19-0.93; P = 0.034）。B2 M高肿瘤显示出免疫细胞和免疫检查点标记物的富集。我们的研究表明，B2 M表达与免疫检查点抑制剂（ICI）治疗的HNSCC的存活率提高相关。在目前的研究中，DSP揭示了在R/M HNSCC中肿瘤区室中B2 M表达与免疫治疗结果的正相关性。
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. In the current study, DSP revealed the positive association of B2M expression in the tumor compartment with immunotherapy outcomes in R/M HNSCC.