Guennoun Ranya, Hojanazarova Jennet, Trerice Kathryn E, Azin Marjan, McGoldrick Matthew T, Schiferle Erik B, Stover Michael P, Demehri Shadmehr
Center for Cancer Immunology, Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cancers (Basel). 2022 Apr 27;14(9):2173. doi: 10.3390/cancers14092173.
Lung cancer is the leading cause of cancer deaths in the United States and across the world. Immunotherapies, which activate tumor-infiltrating cytotoxic T lymphocytes, have demonstrated efficacy for the treatment of advanced-stage lung cancer. However, the potential for harnessing the immune system against the early stages of lung carcinogenesis to prevent cancer development and recurrence remains unexplored. Using a mouse model of lung adenocarcinoma, we investigated the effects of thymic stromal lymphopoietin (TSLP) induction on early cancer development in the lungs. Herein, we demonstrate that systemic TSLP induction suppressed spontaneous lung cancer development in Kras mice. TSLP drove a significant CD4 T cell response to block lung cancer progression from atypical alveolar hyperplasia to adenocarcinoma. Our findings suggest that TSLP can be used in the early stages of lung cancer development to trigger a lasting immunity in the tissue and prevent the development of advanced disease.
肺癌是美国乃至全球癌症死亡的主要原因。激活肿瘤浸润性细胞毒性T淋巴细胞的免疫疗法已证明对晚期肺癌的治疗有效。然而，利用免疫系统对抗肺癌发生早期阶段以预防癌症发展和复发的潜力仍未得到探索。我们使用肺腺癌小鼠模型，研究了胸腺基质淋巴细胞生成素（TSLP）诱导对肺部早期癌症发展的影响。在此，我们证明全身TSLP诱导可抑制Kras小鼠自发性肺癌的发展。TSLP引发了显著的CD4 T细胞反应，以阻止肺癌从非典型肺泡增生发展为腺癌。我们的研究结果表明，TSLP可用于肺癌发展的早期阶段，以在组织中触发持久免疫并预防晚期疾病的发展。
