Case Report: Tumor Microenvironment Characteristics in a Patient With HER2 Mutant Lung Squamous Cell Carcinoma Harboring High PD-L1 Expression Who Presented Hyperprogressive Disease.
Case Report: Tumor Microenvironment Characteristics in a Patient With HER2 Mutant Lung Squamous Cell Carcinoma Harboring High PD-L1 Expression Who Presented Hyperprogressive Disease.
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病例报告：PD-L1 高表达的 HER2 突变肺鳞状细胞癌患者的肿瘤微环境特征，且病情进展过度
DOI：
10.3389/fonc.2021.760703
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发表时间：
2021
影响因子：
4.7
通讯作者：
Xia Y
中科院分区：
文献类型：
--
作者：
Xia L;Yu Y;Lan F;Yan J;Li J;Li W;Xia Y
PD-L1在非小细胞肺癌（NSCLC）中的高表达显然可以预测免疫治疗疗效的提高，而具有致癌驱动基因突变的NSCLC的免疫治疗效果较差。因此，研究在同时存在高PD-L1表达和驱动基因突变的情况下免疫单一疗法的有效性是非常有意义的。患者和方法我们报告了一例PD-L1高表达和HER 2 20号外显子插入（20 Ins）的鳞状细胞肺癌，在接受PD-1抑制剂治疗后出现高进展性疾病（HPD）。结果1例71岁女性患者确诊为晚期肺鳞癌，肿瘤比例评分PD-1为98%，INS为20。她从一线多西他赛顺铂治疗中获益，随后接受2个月二线阿法替尼治疗。然后给予三线pembrolizumab单药治疗。不幸的是，她迅速进展，原发部位以及纵隔淋巴结和胸腔积液急剧扩大，仅2周后，出现严重的呼吸困难和吞咽困难。再次进行活检，我们发现与基线相比，CD 8 + T细胞仅在肿瘤间质中大量募集，而不在肿瘤实质中募集。肿瘤相关巨噬细胞在肿瘤间质和实质中均显著增加。同时，肿瘤实质中的CD 56 dim NK细胞减少。结论在具有阳性驱动基因的患者中应用免疫单药治疗需要非常谨慎，即使具有高PD-L1表达。肿瘤微环境的异常可能是免疫检查点启动子诱导HPD的重要机制。需要进行更深入的研究。
Background High PD-L1 expression in non-small cell lung cancer (NSCLC) is evident to predict elevated immunotherapy efficacy, to which NSCLC with onco-driver gene mutations is probed with poor responsiveness. Thus, it is of great interest to investigate how effective immune monotherapy is in the presence of concurrent high PD-L1 expression and driving gene mutation. Patients and methods We present a case of squamous lung cancer with high PD-L1 expression and HER2 exon 20 insertion (20Ins) who presented hyperprogressive disease (HPD) after being treated with PD-1 inhibitor. Results A 71-year-old female was diagnosed with advanced squamous lung cancer with 98% tumor proportion score of PD-1 and 20ins. She benefited from first-line docetaxel cisplatin followed by 2 months second-line afatinib. Third-line pembrolizumab monotherapy was then given. Unfortunately, she rapidly progressed with dramatically enlarged primary site as well as mediastinal lymph nodes and pleural effusion only 2 weeks later, presenting severe dyspnea and dysphagia. Re-biopsy was conducted, and we found that compared with the baseline, CD8+ T cells were largely recruited only in tumor stroma but not in tumor parenchyma. Tumor-associated macrophages were notably increased in both tumor stroma and parenchyma. Concomitantly, CD56dim NK cells in tumor parenchyma were decreased. Conclusions Application of immune monotherapy in patients with positive driver genes demands extreme caution, even harboring high PD-L1 expression. Abnormality of tumor microenvironment might be critically involved in immune checkpoint inhibitor-induced HPD. Further study in greater depth is required.
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影响因子：
16.6
作者：
Koyama S;Akbay EA;Li YY;Herter-Sprie GS;Buczkowski KA;Richards WG;Gandhi L;Redig AJ;Rodig SJ;Asahina H;Jones RE;Kulkarni MM;Kuraguchi M;Palakurthi S;Fecci PE;Johnson BE;Janne PA;Engelman JA;Gangadharan SP;Costa DB;Freeman GJ;Bueno R;Hodi FS;Dranoff G;Wong KK;Hammerman PS
通讯作者：
Hammerman PS
DOI：
10.1158/1078-0432.ccr-16-3133
发表时间：
2017-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kato S;Goodman A;Walavalkar V;Barkauskas DA;Sharabi A;Kurzrock R
通讯作者：
Kurzrock R
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
3.6
作者：
Lau, Sally C. M.;Fares, Aline Fusco;Sacher, Adrian G.
通讯作者：
Sacher, Adrian G.
阿法替尼治疗 HER2 突变非小细胞肺癌患者的疗效：荟萃分析
影响因子：
0.9
作者：
Zhou N;Zhao J;Huang X;Shen H;Li W;Xu Z;Xia Y
通讯作者：
Xia Y