生物标志物是必要的，以识别在接受明确疗法之前可能对新辅助免疫治疗（NIT）做出反应的患者。我们假设，肿瘤细胞HLA I类的表达与未经治疗的原发头颈癌NIT后的病理学反应（PR）相关。利用多光谱免疫荧光技术，对使用双重TGF-β和PD-L1抑制剂bintrafusp alfa进行新辅助研究的患者的术前和术后活检标本进行了检测。观察到肿瘤细胞HLA I类和PD-L1的不一致表达，大部分阳性肿瘤细胞表达HLA I类或PD-L1，但不是同时表达。空间分析显示，肿瘤实质T细胞和HLA I阳性肿瘤细胞之间存在共定位，但T细胞和PD-L1阳性肿瘤细胞之间没有明确的共定位。较大的术前肿瘤细胞HLA I类表达，但不是PD-L1表达或肿瘤T细胞浸润，与PR的发展有关。此外，NIT后肿瘤细胞HLA I类表达的增加与PR的发展相关，而治疗后PD-L1和T细胞浸润的变化不确定。这些数据支持对肿瘤细胞HLA I类表达进行更大的前瞻性研究，以确定在接受NIT的新诊断HNSCC患者中PR的生物标志物的性能。由Elsevier Ltd.发表。

Biomarkers are needed to identify patients likely to respond to neoadjuvant immunotherapy (NIT) prior to receiving definitive treatment.We hypothesized that expression of tumor cell HLA class I would correlate with pathologic response (PR) following NIT for primary untreated head and neck cancer. Multispectral immunofluorescence of pre- and post-treatment biopsy specimens from a neoadjuvant study of bintrafusp alfa, a dual TGF-β and PD-L1 inhibitor, was performed.Discordant expression of tumor cell HLA class I and PD-L1 measured by multispectral immunofluorescence was observed with most positive tumor cells expressing HLA class I or PD-L1 but not both. Spatial analysis revealed colocalization between tumor parenchyma T cells and HLA class I positive tumors cells, but no clear colocalization between T cells and PD-L1 positive tumor cells. Greater pre-treatment tumor cell HLA class I expression, but not PD-L1 expression or tumor T cell infiltration, correlated with the development of a PR. Additionally, increased tumor cell HLA class I expression after NIT compared to before NIT correlated with development of a PR, whereas inconsistent changes in PD-L1 and T cell infiltration were observed after treatment in all patients.These data provide the rationale for the study of tumor cell HLA class I expression in larger prospective studies powered to determine the performance of biomarkers of PR in newly diagnosed HNSCC patients receiving NIT.Published by Elsevier Ltd.