一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
帕博利珠单抗治疗的非小细胞肺癌的肿瘤特征和治疗反应性
英文原题：Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.
查看英文原题
Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.
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中文摘要
帕博利珠单抗是一种广泛使用的免疫检查点抑制剂（ICI），已彻底改变了非小细胞肺癌（NSCLC）的治疗。识别可能对帕博利珠单抗产生应答的患者的独特肿瘤特征，有助于临床判断和个性化治疗策略的制定。在这项回顾性研究中，我们回顾了84例接受帕博利珠单抗治疗的NSCLC患者的临床数据和病理特征。
我们检查了临床和人口学特征与免疫治疗前获得的肿瘤组织病理学特征之间的相关性。帕博利珠单抗治疗的应答通过实体瘤疗效评价标准（RECIST）进行评估。根据以下RECIST将临床数据和癌组织特征在三组之间进行评估和比较：应答组（RG）、疾病稳定组（SD）和疾病进展组（PD），其中RG包括完全缓解（CR）或部分缓解（PR）的患者。RG组的总生存率显著高于SD组和PD组。
此外，RG组和SD组治疗前存活肿瘤细胞含量的百分比显著更高。同时，细胞外间质比例显著低于PD组。RG组中TIL（肿瘤浸润淋巴细胞）（TILs）的数量显著高于PD组。在肿瘤坏死、间质组成、PD-L1表达水平（TPS 1-49% vs. ≥50%）和治疗应答方面没有显著差异。
总之，与SD或PD患者相比，对pembrolizumab治疗有阳性反应的NSCLC患者群体预后更好。此外，存活肿瘤细胞与肿瘤相关淋巴细胞的相对比例与治疗反应性相关。预计更大规模的前瞻性临床研究将进一步验证这些发现。
展开英文摘要原文
Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical adjudication and development of a personalized therapeutic strategy. In this retrospective study, we reviewed the clinical data and pathological features of 84 NSCLC patients treated with pembrolizumab.
We examined the correlation between the clinical and demographic characteristics and the tumor histopathologic features obtained before immunotherapy. The response to pembrolizumab therapy was evaluated via the Response Evaluation Criteria in Solid Tumors (RECIST).
The clinical data and cancer tissue characteristics were assessed and compared among three groups according to the following RECIST: the responsive group (RG), the stable disease group (SD), and the progressive disease group (PD), where the RG comprised patients with either a complete response (CR) or a partial response (PR). The overall survival rate of the RG group was significantly higher than the SD and PD groups.
In addition, the percentage of pre-treatment viable tumor cell content in the RG and SD groups was significantly higher. At the same time, the extracellular stroma proportion was significantly lower than that of the PD group. The number of tumor-infiltrating lymphocytes (TILs) in the RG group was significantly higher than in the PD group. There were no significant differences in tumor necrosis, the stroma composition, PD-L1 expression level (TPS 1-49% vs. ≥50%), and treatment response.
In conclusion, our population of NSCLC patients who experienced positive treatment responses to pembrolizumab therapy had a better prognosis compared to patients with either SD or PD.
Moreover, the relative proportions of viable tumor cells to tumor-associated lymphocytes were associated with responsiveness to treatment. It is expected that larger prospective clinical studies will further validate these findings.
论文信息
- 作者
- Li H、Shyam Sunder S、Jatwani K、Bae Y、Deng L、Liu Q、Dy GK、Pokharel S
- 单位
- Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.United States
- 期刊
- Cancers2024 Feb 10
- 原文标识
- PubMed 38398135 · DOI 10.3390/cancers16040744
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