Farrugia Mark K, Repasky Elizabeth A, Chen Minhui, Attwood Kristopher, Catalfamo Kayla, Rosenheck Hanna, Yao Song, Mattson David M, Mukherjee Sarbajit, Kukar Moshim, Witkiewicz Agnieszka K, Singh Anurag K
Departments of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
Departments of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Cancer Immunol Immunother. 2025 Jan 3;74(2):57. doi: 10.1007/s00262-024-03891-3.
Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication. We investigated whether the immune landscape of pretreatment tissue was associated with relapse in ESC patients.
Between April 2010 and October 2018, we identified 25 patients who had undergone trimodal therapy for ESC and had pretreatment biopsies suitable for analyses. We performed high-throughput multispectral immunofluorescence (mIF) analysis on formalin-fixed paraffin embedded biopsy samples. Analysis of 27 unique populations via immune and exhaustion mIF panels was performed and expression was normalized to total cell counts.
Of the 25 patients analyzed, the median follow-up time was 23.9 months, during which 12 (48%) patients suffered a relapse with a median time to progression of 13.1 months. mIF revealed higher expression of HLA-DR (p = 0.019), CD8/LAG3 (p = 0.046), and CD8/CTLA4 (p = 0.027) among patients without relapse. Time to progression (TTP) and disease-specific survival (DSS) were stratified by median expression of each significant subpopulation and formally tested by the log-rank test. Higher than median expression of HLA-DR (p = 0.027), CD8/LAG3 (p = 0.039), and CD8/CTLA4 (p = 0.039) were significantly associated with TTP. Similarly, HLA-DR (p = 0.0069) and CD8/CTLA4 (p = 0.036) were significantly associated with improved DSS, whereas no significant observations were found with CD8/LAG3 (p = 0.11) expression. Stromal, but not tumoral expression of CD163 and CD163/PDL1 were significantly associated with improved TTP and DSS.
High expression of HLA-DR, CD8/CTLA4, and stromal expression of CD163 and CD163/PDL1 within pretreatment biopsy ESC samples was associated with significantly reduced rates of relapse. Increased presence of these markers suggests that an improved immune landscape is associated with less aggressive disease and may provide an opportunity for risk-based treatment strategies.
食管癌（ESC）是一种侵袭性疾病，通常在晚期出现。尽管采用了三联疗法，但40%-50%的患者在18个月内可能会发生转移性疾病。识别有转移扩散风险的患者具有挑战性，需要改进预后评估。我们研究了治疗前组织的免疫格局是否与ESC患者的复发有关。
在2010年4月至2018年10月期间，我们确定了25例接受过ESC三联疗法且有适合分析的治疗前活检样本的患者。我们对福尔马林固定石蜡包埋的活检样本进行了高通量多光谱免疫荧光（mIF）分析。通过免疫和耗竭mIF面板对27个独特群体进行了分析，并将表达量标准化为总细胞计数。
在分析的25例患者中，中位随访时间为23.9个月，在此期间，12例（48%）患者复发，中位进展时间为13.1个月。mIF显示，未复发患者中HLA-DR（p = 0.019）、CD8/LAG3（p = 0.046）和CD8/CTLA4（p = 0.027）的表达较高。进展时间（TTP）和疾病特异性生存（DSS）按每个显著亚群的中位表达进行分层，并通过对数秩检验进行正式检验。HLA-DR（p = 0.027）、CD8/LAG3（p = 0.039）和CD8/CTLA4（p = 0.039）高于中位表达与TTP显著相关。同样，HLA-DR（p = 0.0069）和CD8/CTLA4（p = 0.036）与改善的DSS显著相关，而CD8/LAG3（p = 0.11）表达未发现显著差异。CD163和CD163/PDL1的基质而非肿瘤表达与改善的TTP和DSS显著相关。
治疗前活检ESC样本中HLA-DR、CD8/CTLA4的高表达以及CD163和CD163/PDL1的基质表达与复发率显著降低相关。这些标志物的增加表明，改善的免疫格局与侵袭性较低的疾病相关，并可能为基于风险的治疗策略提供机会。
