Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy.
Int J Mol Sci. 2021 Oct 15;22(20):11123. doi: 10.3390/ijms222011123.
Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.
小细胞肺癌(SCLC)是一种侵袭性恶性肿瘤,具有快速倍增时间、高生长分数和广泛转移的早期发展。免疫检查点抑制剂在一线化疗中的加入代表了几十年来系统治疗的首次重大进展。然而,与非小细胞肺癌的作用相比,免疫治疗的加用效果在 SCLC 中并不明显。具体来说,只有少数 SCLC 患者受益于免疫检查点抑制剂。此外,SCLC 缺乏生物标志物选择,临床试验主要集中在未选择的人群上。在这里,我们回顾了有关免疫治疗主要生物标志物的数据,即程序性死亡配体 1 表达和肿瘤突变负担。此外,我们还探讨了其他潜在的生物标志物,包括 SCLC 中免疫微环境的作用、遗传改变的作用以及神经副肿瘤综合征、血清抗神经元核抗体与接受免疫治疗的 SCLC 患者结局之间的潜在联系。