Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 108 Biomedical Drive, Morgantown, WV, 26506, USA.
Rockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, USA.
Cancer Immunol Immunother. 2024 Jan 19;73(1):20. doi: 10.1007/s00262-023-03599-w.
Lung cancer is the most common primary tumor to metastasize to the brain. Although advances in lung cancer therapy have increased rates of survival over the past few decades, control and treatment of lung cancer brain metastasis remains an urgent clinical need. Herein, we examine the temporal coordination of α-CTLA-4 administration in combination with whole-brain radiation therapy in a syngeneic preclinical model of lung cancer brain metastasis in both C57Bl/6 and athymic nude mice. Brain tumor burden, survival, and weight loss were monitored. Immunotherapy administration 24 h prior to irradiation resulted in increased brain tumor burden, while administration of immunotherapy 12 h after radiation decreased tumor burden. Neither of the treatments affected survival outcomes or weight loss due to brain tumor recurrence. These findings suggest that the coordination of α-CTLA-4 administration in addition to whole-brain radiation therapy may be a viable strategy for reduction of tumor burden for the management of lung cancer brain metastasis.
肺癌是最常见的向脑部转移的原发性肿瘤。尽管过去几十年肺癌治疗的进展提高了生存率，但肺癌脑转移的控制和治疗仍然是一个迫切的临床需求。在此，我们在 C57Bl/6 和无胸腺裸鼠的肺癌脑转移的同源临床前模型中，检查 α-CTLA-4 联合全脑放疗的时间协调。监测脑肿瘤负担、存活率和体重减轻。免疫治疗在照射前 24 小时给药会导致脑肿瘤负担增加，而在放射治疗后 12 小时给药会减少肿瘤负担。两种治疗方法都不会影响由于脑肿瘤复发导致的生存结果或体重减轻。这些发现表明，除了全脑放疗外，α-CTLA-4 给药的协调可能是减少肺癌脑转移瘤负担的一种可行策略。
