Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Department of Radiation Oncology, Ajou University Medical Center, Suwon, Korea.
Cancer Res Treat. 2021 Oct;53(4):962-972. doi: 10.4143/crt.2020.1053. Epub 2021 Jan 26.
Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.
A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.
Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. -0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.
IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.
辐射诱导的淋巴细胞减少与实体瘤的不良结局相关。我们评估了白细胞介素 7（IL-7）——淋巴细胞稳态的关键细胞因子——对辐射诱导的淋巴细胞减少的影响。
对 2016 年至 2018 年接受放疗的 98 例肝细胞癌患者的前瞻性队列进行了一项事后分析。在放疗前后检测血液中的 IL-7 水平。急性重度淋巴细胞减少症（ASL）定义为放疗期间总淋巴细胞计数<200/μL。采用 Cox 和逻辑回归分析分别确定生存和 ASL 发展的预测因素。
发生 ASL（n=41）的患者总生存率显著低于未发生者（12.0 个月 vs. 25.3 个月，p=0.001）。淋巴细胞恢复的患者总生存率显著长于未恢复者（21.8 个月 vs. 10.3 个月，p=0.042）。ASL 是不良生存的独立预测因素（风险比，2.07；p=0.015）。发生 ASL 的患者放疗前 IL-7 水平显著较低（2.07 pg/mL vs. 3.01 pg/mL，p=0.010）。放疗前高 IL-7 水平是降低 ASL 发生风险的独立预测因素（风险比，0.40；p=0.004）。IL-7 水平反映了对 ASL 的反馈反应，ASL 患者的ΔIL-7 较高（0.48 pg/mL vs. -0.66 pg/mL，p<0.001），而无 ASL 患者的ΔIL-7 较低。放疗后 IL-7 水平与 2 个月时的总淋巴细胞计数呈显著正相关。
IL-7 与 ASL 的发生和恢复相关，可能影响生存。为了克服辐射诱导的淋巴细胞减少，可以考虑使用 IL-7 的新策略。
