| Citation: |
WANG Yue, ZHU Hui. Research Development of Radiation-Induced Lymphopenia[J]. Cancer Research on Prevention and Treatment, 2025, 52(4): 337-341. DOI: 10.3971/j.issn.1000-8578.2025.24.0998
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When radiotherapy is administered, many patients exhibit a reduction in lymphocyte numbers due to the inherent radio-sensitivity of lymphocytes. In particular, they experience a decrease in CD8+ T cells, which may weaken their mediated antitumor immune response. While radiotherapy activates the immune system, it can also lead to a certain degree of immunosuppression. Current research suggests that the formation mechanism of radiation-induced lymphopenia (RIL) involves multiple factors, including increased radiation exposure to lymphocytes and the application of lymphocytotoxic drugs. The adverse impact of RIL on patients’ clinical outcomes can be mitigated, to some extent, by actively optimizing radiotherapy dosimetric parameters to maximally protect lymphocytes.
Competing interests: The authors declare that they have no competing interests.
| [1] |
Mao YP, Zhou GQ, Liu LZ, et al. Comparison of radiological and clinical features of temporal lobe necrosis in nasopharyngeal carcinoma patients treated with 2D radiotherapy or intensity-modulated radiotherapy[J]. Br J Cancer, 2014, 110(11): 2633-2639. doi: 10.1038/bjc.2014.243
|
| [2] |
Kam MK, Chau RM, Suen J, et al. Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation[J]. Int J Radiat Oncol Biol Phys, 2003, 56(1): 145-157. doi: 10.1016/S0360-3016(03)00075-0
|
| [3] |
Nakamura N, Kusunoki Y, Akiyama M. Radiosensitivity of CD4 or CD8 positive human T-lymphocytes by an in vitro colony formation assay[J]. Radiat Res, 1990, 123(2): 224-227. doi: 10.2307/3577549
|
| [4] |
Joseph N, McWilliam A, Kennedy J, et al. Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy[J]. Radiother Oncol, 2019, 135: 115-119. doi: 10.1016/j.radonc.2019.03.008
|
| [5] |
Cho Y, Park S, Byun HK, et al. Impact of Treatment-Related Lymphopenia on Immunotherapy for Advanced Non-Small Cell Lung Cancer[J]. Int J Radiat Oncol Biol Phys, 2019, 105(5): 1065-1073. doi: 10.1016/j.ijrobp.2019.08.047
|
| [6] |
Upadhyay R, Venkatesulu BP, Giridhar P, et al. Risk and impact of radiation related lymphopenia in lung cancer: A systematic review and meta-analysis[J]. Radiother Oncol, 2021, 157: 225-233. doi: 10.1016/j.radonc.2021.01.034
|
| [7] |
Tang C, Liao Z, Gomez D, et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes[J]. Int J Radiat Oncol Biol Phys, 2014, 89(5): 1084-1091. doi: 10.1016/j.ijrobp.2014.04.025
|
| [8] |
Rudra S, Hui C, Rao YJ, et al. Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma[J]. Int J Radiat Oncol Biol Phys, 2018, 101(1): 217-225. doi: 10.1016/j.ijrobp.2018.01.069
|
| [9] |
Kroese TE, Jairam J, Ruurda JP, et al. Severe lymphopenia acquired during chemoradiotherapy for esophageal cancer: Incidence and external validation of a prediction model[J]. Radiother Oncol, 2021, 163: 192-198. doi: 10.1016/j.radonc.2021.08.009
|
| [10] |
Liu J, Zhao Q, Deng W, et al. Radiation-related lymphopenia is associated with spleen irradiation dose during radiotherapy in patients with hepatocellular carcinoma[J]. Radiat Oncol, 2017, 12(1): 90. doi: 10.1186/s13014-017-0824-x
|
| [11] |
Taguchi A, Furusawa A, Ito K, et al. Postradiotherapy persistent lymphopenia as a poor prognostic factor in patients with cervical cancer receiving radiotherapy: a single-center, retrospective study[J]. Int J Clin Oncol, 2020, 25(5): 955-962. doi: 10.1007/s10147-020-01623-y
|
| [12] |
Yu H, Chen F, Lam KO, et al. Potential Determinants for Radiation-Induced Lymphopenia in Patients With Breast Cancer Using Interpretable Machine Learning Approach[J]. Front Immunol, 2022, 13: 768811. doi: 10.3389/fimmu.2022.768811
|
| [13] |
de Kermenguy F, Meziani L, Mondini M, et al. Radio-induced lymphopenia in the era of anti-cancer immunotherapy[J]. Int Rev Cell Mol Biol, 2023, 378: 1-30.
|
| [14] |
Yang TJ, Oh JH, Apte A, et al. Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy[J]. Radiother Oncol, 2014, 113(1): 29-34. doi: 10.1016/j.radonc.2014.09.002
|
| [15] |
Pike LRG, Bang A, Mahal BA, et al. The Impact of Radiation Therapy on Lymphocyte Count and Survival in Metastatic Cancer Patients Receiving PD-1 Immune Checkpoint Inhibitors[J]. Int J Radiat Oncol Biol Phys, 2019, 103(1): 142-151. doi: 10.1016/j.ijrobp.2018.09.010
|
| [16] |
Lee BM, Byun HK, Seong J. Significance of lymphocyte recovery from treatment-related lymphopenia in locally advanced pancreatic cancer[J]. Radiother Oncol, 2020, 151: 82-87. doi: 10.1016/j.radonc.2020.07.026
|
| [17] |
Cho Y, Kim Y, Chamseddine I, et al. Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage Ⅲ NSCLC patients undergoing maintenance immunotherapy[J]. Radiother Oncol, 2022, 168: 1-7. doi: 10.1016/j.radonc.2022.01.007
|
| [18] |
Harisiadis L, Kopelson G, Chang CH. Lymphopenia caused by cranial irradiation in children receiving craniospinal radiotherapy[J]. Cancer, 1977, 40(3): 1102-1108. doi: 10.1002/1097-0142(197709)40:3<1102::AID-CNCR2820400319>3.0.CO;2-0
|
| [19] |
Zhao Q, Li T, Du S, et al. Shortened Radiation Time Promotes Recovery From Radiation-induced Lymphopenia in Early-Stage Non-small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy[J]. Technol Cancer Res Treat, 2022, 21: 15330338221112287.
|
| [20] |
Verastegui EL, Morales RB, Barrera-Franco JL, et al. Long-term immune dysfunction after radiotherapy to the head and neck area[J]. Int Immunopharmacol, 2003, 3(8): 1093-1104. doi: 10.1016/S1567-5769(03)00013-4
|
| [21] |
McLaughlin M, Patin EC, Pedersen M, et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy[J]. Nat Rev Cancer, 2020, 20(4): 203-217. doi: 10.1038/s41568-020-0246-1
|
| [22] |
Pointer KB, Pitroda SP, Weichselbaum RR. Radiotherapy and immunotherapy: open questions and future strategies[J]. Trends Cancer, 2022, 8(1): 9-20. doi: 10.1016/j.trecan.2021.10.003
|
| [23] |
Cha JH, Chan LC, Li CW, et al. Mechanisms Controlling PD-L1 Expression in Cancer[J]. Mol Cell, 2019, 76(3): 359-370. doi: 10.1016/j.molcel.2019.09.030
|
| [24] |
Ding XC, Wang LL, Zhang XD, et al. The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia[J]. J Hematol Oncol, 2021, 14(1): 92. doi: 10.1186/s13045-021-01102-5
|
| [25] |
Wang NH, Lei Z, Yang HN, et al. Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review[J]. Ann Transl Med, 2022, 10(24): 1406. doi: 10.21037/atm-22-6049
|
| [26] |
Sanchez-Perez L, Suryadevara CM, Choi BD, et al. Leveraging chemotherapy-induced lymphopenia to potentiate cancer immunotherapy[J]. Oncoimmunology, 2014, 3(7): e944054. doi: 10.4161/21624011.2014.944054
|
| [27] |
Chen F, Ma L, Wang Q, et al. Chemotherapy is a risk factor of lymphopenia before adjuvant radiotherapy in breast cancer[J]. Cancer Rep (Hoboken), 2022, 5(7): e1525. doi: 10.1002/cnr2.1525
|
| [28] |
Li YD, Lamano JB, Kaur G, et al. Lymphopenia predicts response to stereotactic radiosurgery in lung cancer patients with brain metastases[J]. J Neurooncol, 2019, 143(2): 337-347. doi: 10.1007/s11060-019-03169-0
|
| [29] |
Kunogi H, Yamaguchi N, Terao Y, et al. Dosimetric predictors of nephrotoxicity in patients receiving extended-field radiation therapy for gynecologic cancer[J]. Radiat Oncol, 2021, 16(1): 25. doi: 10.1186/s13014-021-01755-z
|
| [30] |
Zhao Q, Bi Y, Xue J, et al. Prognostic value of absolute lymphocyte count in patients with advanced esophageal cancer treated with immunotherapy: a retrospective analysis[J]. Ann Transl Med, 2022, 10(13): 744. doi: 10.21037/atm-22-2669
|
| [31] |
Reddy AV, Deek MP, Jackson JF, et al. Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy[J]. Radiat Oncol, 2021, 16(1): 242. doi: 10.1186/s13014-021-01969-1
|
| [32] |
Byun HK, Kim N, Yoon HI, et al. Clinical predictors of radiation-induced lymphopenia in patients receiving chemoradiation for glioblastoma: clinical usefulness of intensity-modulated radiotherapy in the immuno-oncology era[J]. Radiat Oncol, 2019, 14(1): 51. doi: 10.1186/s13014-019-1256-6
|
| [33] |
Abravan A, Faivre-Finn C, Kennedy J, et al. Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer[J]. J Thorac Oncol, 2020, 15(10): 1624-1635. doi: 10.1016/j.jtho.2020.06.008
|
| [34] |
Park S, Byun HK, Seong J. Irradiation-Related Lymphopenia for Bone Metastasis from Hepatocellular Carcinoma[J]. Liver Cancer, 2019, 8(6): 468-479. doi: 10.1159/000500461
|
| [35] |
Gonuguntla S, Herz J. Unraveling the lymphatic system in the spinal cord meninges: a critical element in protecting the central nervous system[J]. Cell Mol Life Sci, 2023, 80(12): 366. doi: 10.1007/s00018-023-05013-1
|
| [36] |
Møllgård K, Beinlich FRM, Kusk P, et al. A mesothelium divides the subarachnoid space into functional compartments[J]. Science, 2023, 379(6627): 84-88. doi: 10.1126/science.adc8810
|
| [37] |
Nguyen TT, Shin DH, Sohoni S, et al. Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry[J]. J Immunother Cancer, 2022, 10(7): e004935. doi: 10.1136/jitc-2022-004935
|
| [38] |
Brenner AW, Patel AJ. Review of Current Principles of the Diagnosis and Management of Brain Metastases[J]. Front Oncol, 2022, 12: 857622. doi: 10.3389/fonc.2022.857622
|
| [39] |
Huang J, DeWees TA, Badiyan SN, et al. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma[J]. Int J Radiat Oncol Biol Phys, 2015, 92(5): 1000-1007. doi: 10.1016/j.ijrobp.2015.04.005
|
| [40] |
Grossman SA, Ye X, Lesser G, et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide[J]. Clin Cancer Res, 2011, 17(16): 5473-5480. doi: 10.1158/1078-0432.CCR-11-0774
|
| [41] |
Raghu D, Xue HH, Mielke LA. Control of Lymphocyte Fate, Infection, and Tumor Immunity by TCF-1[J]. Trends Immunol, 2019, 40(12): 1149-1162. doi: 10.1016/j.it.2019.10.006
|
| [42] |
Uzhachenko RV, Shanker A. CD8+ T Lymphocyte and NK Cell Network: Circuitry in the Cytotoxic Domain of Immunity[J]. Front Immunol, 2019, 10: 1906. doi: 10.3389/fimmu.2019.01906
|
| [43] |
Kim WJ, Dho YS, Ock CY, et al. Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma[J]. J Neurooncol, 2019, 143(2): 321-328. doi: 10.1007/s11060-019-03167-2
|
| [44] |
Wang X, Lu J, Teng F, et al. Lymphopenia association with accelerated hyperfractionation and its effects on limited-stage small cell lung cancer patients' clinical outcomes[J]. Ann Transl Med, 2019, 7(16): 385. doi: 10.21037/atm.2019.07.58
|
| [45] |
Shiraishi Y, Fang P, Xu C, et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy[J]. Radiother Oncol, 2018, 128(1): 154-160.
|
| [46] |
Wang Y, Zeng W, Xie W, et al. Lymphopenia associated with whole-brain radiotherapy and its effects on clinical outcomes of patients with brain metastases[J]. Sci Rep, 2024, 14(1): 21315. doi: 10.1038/s41598-024-71943-w
|
| [47] |
Chen D, Patel RR, Verma V, et al. Interaction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapy[J]. Radiother Oncol, 2020, 150: 114-120. doi: 10.1016/j.radonc.2020.05.051
|
| [48] |
Wang Q, Qiu Q, Zhang Z, et al. Bone marrow dosimetric analysis of lymphopenia in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy[J]. Cancer Med, 2021, 10(17): 5847-5858. doi: 10.1002/cam4.4131
|
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