病例报告:使用辅助免疫疗法后,肺癌自发缓解,但晚期出现复发:异常的肿瘤微环境。
Case report: Spontaneous remission in lung carcinoma with a late relapse after adjuvant immunotherapy: Exceptional tumor micro-environment.
发表日期:2023
作者:
Yan Chen, Wenhui Guan, Changhao Zhong, Jiaxi Deng, Minjuan Hu, Wenwei Mo, Xiaohong Xie, Shiyue Li, Chengzhi Zhou, Xinqing Lin
来源:
Frontiers in Immunology
摘要:
免疫辅助治疗后局部复发自发性消退(SR)的报道很少,其潜在机制尚不清楚。本文报道了一例接受尼伏单抗联合化疗的cT2aN2M0期鳞状细胞性肺癌患者。该患者在最后一次治疗剂量七个月后,在心下淋巴结经历了迟发性复发,但在接下来的三个月内未经任何抗肿瘤治疗就取得了SR,完全缓解持续了至今11个月。值得注意的是,在复发期间,患者的支气管肺泡灌洗液中检测到大量的致病微生物,但在SR后消失了。此外,患者经历了淋巴结穿刺引起的发热,但没有其他症状。通过多重免疫荧光和全转录组测序对复发淋巴结中渗透的免疫细胞进行了纵向分析,发现在初次复发时CD8+T细胞被招募到基质区域,然后迁移到肿瘤组织,并在肿瘤细胞消除后继续增加。同时,CD8+T细胞的初始招募与较高比例的B细胞相关,丰富的中性粒细胞群体与CD8+T细胞进入肿瘤细胞同时出现。这是关于接受免疫检查点抑制剂(ICI)治疗后迟发性复发但达到SR的非小细胞肺癌(NSCLC)患者的首次报道。我们的病例突显了抗肿瘤免疫的复杂性和可塑性,并有望有助于找到有效对抗ICI治疗抵抗所需的策略。Copyright © 2023 Chen, Guan, Zhong, Deng, Hu, Mo, Xie, Li, Zhou and Lin.
Spontaneous remission (SR) of local recurrence after adjuvant immunotherapy has rarely been reported, and the underlying mechanism is poorly understood. Herein, we reported a patient with stage cT2aN2M0 squamous cell lung carcinoma who received neoadjuvant and adjuvant treatment with nivolumab plus chemotherapy. The patient experienced a late relapse in the subcarinal lymph node seven months after the last dosage of treatment but achieved SR in the next three months without additional antitumor therapy. The complete response lasted for eleven months and counting. Notably, high copies of pathogenic microorganisms were detected in the patient's bronchoalveolar lavage fluid along with the recurrence but disappeared after SR. The patient also experienced a lymph node puncture-induced fever but had no other symptoms. A longitudinal analysis of infiltrated immune cells in the recurrent lymph node was performed by multiplex immunofluorescence and whole transcriptome sequencing, which revealed that CD8+ T cells were recruited during the initial relapse, specifically in the stromal area, then migrated into the tumor tissue, and continued to increase after elimination of tumor cells. Meanwhile, the initial recruitment of CD8+ T cells was coupled with a higher proportion of B cells, and the abundant neutrophil population was synchronous with the infiltration of CD8+ T cells into tumor cells. This is the first report on an Non-small cell lung cancer (NSCLC) patient with a late relapse after adjuvant immune checkpoint inhibitor (ICI) therapy who achieved SR. Our case highlights the complexity and plasticity of antitumor immunity and is expected to help find efficient strategies against the resistance of ICI treatment.Copyright © 2023 Chen, Guan, Zhong, Deng, Hu, Mo, Xie, Li, Zhou and Lin.