Cancer Res Treat.  2021 Oct;53(4):962-972. 10.4143/crt.2020.1053.

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort

  • 1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
  • 2Department of Radiation Oncology, Ajou University Medical Center, Suwon, Korea


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.
Materials and Methods
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.


Interleukin-7; Lymphocyte count; Lymphopenia; Radiotherapy


  • Fig. 1 (A) Changes in the mean (standard deviation) total lymphocyte count (TLC) over time after the initiation of radiotherapy (RT). (B) Overall survival according to the presence of acute severe lymphopenia (ASL). (C) Progression-free survival according to the presence of ASL. (D, E) Overall survival according to the presence of ASL and the recovery from lymphopenia at 2 months after the initiation of RT.

  • Fig. 2 Relationship between interleukin-7 (IL-7) levels and radiation-induced lymphopenia. (A) Pre-radiotherapy (RT) IL-7 levels according to the presence of acute severe lymphopenia (ASL). (B) Changes in IL-7 levels (ΔIL-7) according to the presence of ASL and pre- and post-RT IL-7 levels in patients with and without ASL. (C) The correlation between pre-RT IL-7 levels and the total lymphocyte count (TLC) nadir during RT. (D) The correlation between the TLC nadir during RT and ΔIL-7. (E) The correlation between post-RT IL-7 levels and the TLC at 2 months after the initiation of RT. CI, confidence interval. *p < 0.05, **p < 0.01, ***p < 0.001.



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