Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Respir Investig. 2024 Nov;62(6):1183-1190. doi: 10.1016/j.resinv.2024.10.008. Epub 2024 Oct 22.
Interstitial pneumonia includes a range of disorders affecting the lung interstitium, significantly impacting life expectancy, especially during acute exacerbations. Concurrently, lung cancer remains a leading cause of cancer-related deaths worldwide. The coexistence of these two conditions presents a formidable challenge, complicating diagnosis, treatment, and prognosis. This review explores the critical issues associated with lung cancer comorbid with interstitial pneumonia, focusing on diagnostic challenges, prognosis, treatment complications, and the lack of effective research tools. Diagnosing lung cancer in patients with interstitial pneumonia is complicated due to overlapping imaging features and the risks associated with biopsies. The prognosis is poorer for patients with both conditions, as interstitial pneumonia promotes a more aggressive lung cancer phenotype. Standard treatment for interstitial pneumonia can inadvertently facilitate lung cancer progression, while anticancer therapies often exacerbate interstitial pneumonia. To address the lack of appropriate research tools, a novel murine model combining orthotopic lung cancer cell transplantation with bleomycin-induced interstitial pneumonia was developed to better understand their interaction. This new murine model successfully mimics the human condition, demonstrating increased tumor growth, metastasis, and alterations in the tumor microenvironment, including elevated tumor-associated macrophages, cancer-associated myofibroblasts, and regulatory T cells, alongside decreased cytotoxic T lymphocytes. Lung cancer comorbid with interstitial pneumonia represents a severe clinical challenge due to diagnostic difficulties and treatment-related complications. The novel murine model offers a valuable tool for future research to develop effective therapies. Dedicated efforts are needed to address this complex pathophysiology to improve patient outcomes.
间质性肺炎包括一系列影响肺间质的疾病,严重影响预期寿命,特别是在急性加重期。同时,肺癌仍然是全球癌症相关死亡的主要原因。这两种情况同时存在带来了巨大的挑战,使诊断、治疗和预后变得复杂。本综述探讨了与间质性肺炎合并肺癌相关的关键问题,重点关注诊断挑战、预后、治疗并发症以及缺乏有效的研究工具。由于重叠的影像学特征和活检相关的风险,间质性肺炎患者肺癌的诊断较为复杂。同时患有这两种疾病的患者预后较差,因为间质性肺炎促进了更具侵袭性的肺癌表型。间质性肺炎的标准治疗可能无意中促进肺癌进展,而抗癌治疗通常会使间质性肺炎恶化。为了解决缺乏适当的研究工具的问题,开发了一种新型的结合原位肺癌细胞移植和博来霉素诱导的间质性肺炎的小鼠模型,以更好地了解它们的相互作用。这种新型的小鼠模型成功模拟了人类的情况,显示出肿瘤生长、转移和肿瘤微环境的改变,包括肿瘤相关巨噬细胞、癌症相关肌成纤维细胞和调节性 T 细胞的增加,以及细胞毒性 T 淋巴细胞的减少。间质性肺炎合并肺癌由于诊断困难和治疗相关并发症,代表了严重的临床挑战。新型小鼠模型为未来的研究提供了一种有价值的工具,以开发有效的治疗方法。需要做出专门的努力来解决这种复杂的病理生理学,以改善患者的预后。