鉴定小细胞肺癌的炎症表型，从而提高抗 PD-L1 抗体和化疗的疗效。
Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy.
机构信息
Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara city, Kanagawa, 252-0375, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
出版信息
Lung Cancer. 2023 May;179:107183. doi: 10.1016/j.lungcan.2023.107183. Epub 2023 Mar 25.
BACKGROUND
Platinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear.
METHODS
We retrospectively reviewed post-surgical limited-stage (LS)-SCLC and ES-SCLC patients treated with atezolizumab plus carboplatin and etoposide (ACE). The association between SCLC subtypes based on transcriptomic data and pathological findings, including CD8-positive tumor-infiltrating lymphocyte (TIL) status, was investigated in the LS-SCLC cohort. The association between the efficacy of ACE therapy, pathological subtypes, and TIL status was evaluated in the ES-SCLC cohort.
RESULTS
The LS-SCLC cohort (N = 48) was classified into four SCLC subtypes (ASCL1 + NEUROD1 [SCLC-A + N, N = 17], POU2F3 [SCLC-P, N = 15], YAP1 [SCLC-Y, N = 10], and inflamed [SCLC-I, N = 6]) based on transcriptomic data. SCLC-I showed enriched immune-related pathways, the highest immune score (CD8A expression and T-cell-inflamed gene expression profiles), and epithelial-mesenchymal transition (EMT), in transcriptional subtypes. Immunohistochemical staining (IHC) showed that SCLC-I had the highest density of CD8-positive TILs in transcriptional subtypes. In the ES-SCLC cohort, the efficacy of ACE therapy did not differ according to pathological subtypes. The progression-free survival (PFS) of TIL patients was significantly longer than that of TIL patients (PFS: 7.3 months vs. 4.0 months, p < 0.001).
CONCLUSION
Tumors with a high density of TILs, which represent the most immunogenic SCLC subtype (SCLC-I), based on transcriptomic data could benefit from ACE therapy.
背景
铂类依托泊苷联合抗程序性细胞死亡配体 1（PD-L1）抗体治疗是广泛期小细胞肺癌（ES-SCLC）的标准治疗方法。然而，与 SCLC 联合治疗疗效相关的患者特征尚不清楚。
方法
我们回顾性分析了接受阿替利珠单抗联合卡铂和依托泊苷（ACE）治疗的手术后局限期（LS）-SCLC 和 ES-SCLC 患者。在 LS-SCLC 队列中，根据转录组数据和病理发现（包括 CD8 阳性肿瘤浸润淋巴细胞（TIL）状态），研究了 SCLC 亚型之间的相关性。在 ES-SCLC 队列中，评估了 ACE 治疗的疗效、病理亚型和 TIL 状态之间的相关性。
结果
LS-SCLC 队列（N=48）根据转录组数据分为 4 种 SCLC 亚型（ASCL1+NEUROD1[SCLC-A+N，N=17]、POU2F3[SCLC-P，N=15]、YAP1[SCLC-Y，N=10]和炎症[SCLC-I，N=6]）。SCLC-I 在转录亚型中表现出丰富的免疫相关途径、最高的免疫评分（CD8A 表达和 T 细胞炎症基因表达谱）和上皮-间充质转化（EMT）。免疫组织化学染色（IHC）显示，在转录亚型中，SCLC-I 的 CD8 阳性 TIL 密度最高。在 ES-SCLC 队列中，ACE 治疗的疗效与病理亚型无关。TIL 阳性患者的无进展生存期（PFS）明显长于 TIL 阴性患者（PFS：7.3 个月比 4.0 个月，p<0.001）。
结论
基于转录组数据，具有高 TIL 密度的肿瘤代表最具免疫原性的 SCLC 亚型（SCLC-I），可能从 ACE 治疗中获益。
Zotero 插件