Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Br J Cancer. 2024 Nov;131(10):1567-1575. doi: 10.1038/s41416-024-02821-5. Epub 2024 Aug 31.
Lung cancer has a significant incidence among the population and, unfortunately, has an unfavourable prognosis in most cases. The World Health Organization (WHO) classifies lung tumours into two subtypes based on their phenotype: the Non-Small Cell Lung Cancer (NSCLC) and the Small Cell Lung Cancer (SCLC). SCLC treatment, despite advances in chemotherapy and radiotherapy, is often unsuccessful for cancer recurrence highlighting the need to develop novel therapeutic strategies. In this review, we describe the genetic landscape and tumour microenvironment that characterize the pathological processes of SCLC and how they are responsible for tumour immune evasion. The immunosuppressive mechanisms engaged in SCLC are critical factors to understand the failure of immunotherapy in SCLC and, conversely, suggest that new signalling pathways, such as cGAS/STING, should be investigated as possible targets to stimulate an innate immune response in this subtype of lung cancer. The full comprehension of the innate immunity of cancer cells is thus crucial to open new challenges for successful immunotherapy in treating SCLC and improving patient outcomes.
肺癌在人群中的发病率很高，不幸的是，在大多数情况下预后不佳。世界卫生组织（WHO）根据其表型将肺肿瘤分为两种亚型：非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）。尽管化疗和放疗有所进展，但 SCLC 的治疗往往因癌症复发而失败，这凸显了开发新的治疗策略的必要性。在这篇综述中，我们描述了 SCLC 的遗传景观和肿瘤微环境，这些特征描述了 SCLC 的病理过程，以及它们如何导致肿瘤免疫逃逸。SCLC 中涉及的免疫抑制机制是理解免疫疗法在 SCLC 中失败的关键因素，相反，这表明新的信号通路，如 cGAS/STING，应该被作为可能的靶点来刺激这种肺癌亚型的先天免疫反应。因此，对癌细胞先天免疫的全面理解对于为治疗 SCLC 和改善患者预后的成功免疫疗法开辟新的挑战至关重要。
