新辅助免疫治疗后肺鳞状细胞癌手术标本病理反应形态学观察

Histopathological features of squamous cell carcinoma of lung neoadjuvant immunotherapy focusing on responses

目的总结分析肺鳞状细胞癌新辅助免疫治疗后的病理形态特征。方法纳入31例接受了新辅助免疫治疗的可切除肺鳞状细胞癌患者,均来自中国医学科肿瘤医院招募的抗PD-1信迪利单抗(Sintilimab)新辅助免疫治疗Ⅰb期临床试验(ChiCTR-OIC-17013726)。根据irPRC标准判读免疫治疗相关病理组织学形态,并根据残存活肿瘤百分比评价病理缓解程度。结果根据原发灶残存活肿瘤百分比分为3种病理缓解程度(完全病理缓解、显著病理缓解和非显著病理缓解),该组病例比例分别是19%(6例)、29%(9例)和52%(16例)。新辅助免疫治疗后肿瘤退变区内可见大量的免疫激活现象(大量的免疫细胞浸润,包括淋巴细胞、浆细胞、泡沫样组织细胞浸润,淋巴细胞聚集现象,三级淋巴样结构)、组织修复的形态特征(包括异物巨细胞、肉芽肿形成、增殖性纤维化和新血管生成)。结论新辅助免疫治疗对肺鳞状细胞癌具有较好的疗效。新辅助免疫治疗后病理评估具有与其机制相一致的独特组织病理形态学特征。

Objective To analyze the pathologic features of responses to neoadjuvant immunotherapy of squamous cell carcinoma(SCC)of the lung.Methods The study included 31 patients with resected lung SCC post neoadjuvant immunotherapy.All patients were recruited from the neoadjuvant anti-PD-1(Sintilimab)phaseⅠb clinical trial(ChiCTR-OIC-17013726).The histopathological morphology and different degrees of pathologic response to immunotherapy were evaluated basing on irPRC standard.Results According to the percentage of residual viable tumor(%RVT),pathologic responses of complete pathologic response(cPR),major pathologic response(MPR)and non-MPR were noted in 19%(n=6),29%(n=9),and 52%(n=16)of patients respectively.In addition,extensive immune activation phenomena(immune cell infiltration,including infiltration of lymphocytes,plasma cells,foamy macrophages,lymphocyte aggregation and tertiary lymphoid structures formation)and tissue repair features(giant cells,granuloma formation,proliferative fibrosis and neovascularization)were observed in tumor regression bed.Conclusions Neoadjuvant immunotherapy has favorable effect on lung SCC.Pathologic assessment of resected lung cancer specimens after neoadjuvant immunotherapy shows unique histopathological features consistent with its mechanism.