Xu Shiting, Shukuya Takehito, Shimamura Shoko, Hayashi Takuo, Sato Yoshihiko, Shiozaki Hitomi, Nishioki Toshihiko, Nishino Koichi, Kato Motoyasu, Hattori Aritoshi, Shimada Naoko, Suzuki Kenji, Kitano Shigehisa, Takahashi Kazuhisa
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Transl Lung Cancer Res. 2024 Mar 29;13(3):666-672. doi: 10.21037/tlcr-23-765. Epub 2024 Mar 27.
Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC.
This case report described a patient with recurrent large cell lung cancer undergoing hyperprogressive disease with pleural and pericardial dissemination shortly after the pembrolizumab rechallenge, although he had a favorable response to the initial pembrolizumab treatment. A lower ratio of CD8 T cells to Foxp3 regulatory T cells was distributed in the cell blocks of pleural and pericardial effusion which were taken after hyperprogressive disease, compared to the resected tumor microenvironment. Neutrophil-to-lymphocyte ratio (NLR) was lower in peripheral blood when the disease was controlled and it rose when the disease progressed. Notably, NLR increased dramatically when hyperprogression occurred.
For the first time, we reported that a patient who showed a favorable response to initial anti-PD-1 treatment underwent hyperprogressive disease when rechallenging the same immunotherapy. The increased Foxp3 regulatory T cells in the tumor microenvironment and the longitudinal change of NLRs in peripheral blood were suggested to be associated with hyperprogressive disease.
超进展性疾病是免疫检查点治疗中观察到的一种意外反应模式，与预后不良相关。对于曾经对程序性细胞死亡蛋白1/程序性细胞死亡配体1（PD-1/PD-L1）抑制剂有反应的非小细胞肺癌（NSCLC）患者，再次使用该抑制剂可能是一种治疗选择。在此，我们报告了1例NSCLC患者再次使用PD-1/PD-L1抑制剂后出现的超进展现象。
本病例报告描述了1例复发性大细胞肺癌患者，在再次使用帕博利珠单抗后不久出现超进展性疾病，并伴有胸膜和心包播散，尽管他对初始帕博利珠单抗治疗反应良好。与切除的肿瘤微环境相比，超进展性疾病后采集的胸腔和心包积液细胞块中CD8 T细胞与Foxp3调节性T细胞的比例较低。疾病得到控制时外周血中性粒细胞与淋巴细胞比值（NLR）较低，疾病进展时该比值升高。值得注意的是，当发生超进展时，NLR急剧增加。
我们首次报告了1例对初始抗PD-1治疗反应良好的患者在再次使用相同免疫治疗时出现超进展性疾病。肿瘤微环境中Foxp3调节性T细胞的增加以及外周血中NLR的纵向变化被认为与超进展性疾病有关。
