Paganetti Harald
Department of Radiation Oncology, Massachusetts General Hospital, Boston MA, United States.
Harvard Medical School, Boston MA, United States.
Front Oncol. 2023 Aug 3;13:1201500. doi: 10.3389/fonc.2023.1201500. eCollection 2023.
It is well known that radiation therapy causes lymphopenia in patients and that this is correlated with a negative outcome. The mechanism is not well understood because radiation can have both immunostimulatory and immunosuppressive effects. How tumor dose conformation, dose fractionation, and selective lymph node irradiation in radiation therapy does affect lymphopenia and immune response is an active area of research. In addition, understanding the impact of radiation on the immune system is important for the design and interpretation of clinical trials combining radiation with immune checkpoint inhibitors, both in terms of radiation dose and treatment schedules. Although only a few percent of the total lymphocyte population are circulating, it has been speculated that their increased radiosensitivity may contribute to, or even be the primary cause of, lymphopenia. This review summarizes published data on lymphocyte radiosensitivity based on human, small animal, and studies. The data indicate differences in radiosensitivity among lymphocyte subpopulations that affect their relative contribution and thus the dynamics of the immune response. In general, B cells appear to be more radiosensitive than T cells and NK cells appear to be the most resistant. However, the reported dose-response data suggest that in the context of lymphopenia in patients, aspects other than cell death must also be considered. Not only absolute lymphocyte counts, but also lymphocyte diversity and activity are likely to be affected by radiation. Taken together, the reviewed data suggest that it is unlikely that radiation-induced cell death in lymphocytes is the sole factor in radiation-induced lymphopenia.
众所周知，放射治疗会导致患者淋巴细胞减少，且这与不良预后相关。其机制尚未完全明确，因为辐射可同时具有免疫刺激和免疫抑制作用。放射治疗中的肿瘤剂量适形、剂量分割以及选择性淋巴结照射如何影响淋巴细胞减少和免疫反应是一个活跃的研究领域。此外，了解辐射对免疫系统的影响对于设计和解释将放射治疗与免疫检查点抑制剂相结合的临床试验至关重要，这在辐射剂量和治疗方案方面均是如此。尽管循环中的淋巴细胞仅占淋巴细胞总数的百分之几，但据推测，它们增加的放射敏感性可能导致淋巴细胞减少，甚至可能是其主要原因。本综述总结了基于人类、小动物以及其他研究发表的关于淋巴细胞放射敏感性的数据。这些数据表明淋巴细胞亚群之间的放射敏感性存在差异，这会影响它们的相对贡献，进而影响免疫反应的动态变化。一般来说，B细胞似乎比T细胞对辐射更敏感，而NK细胞似乎最具抗性。然而，报告的剂量反应数据表明，在患者淋巴细胞减少的情况下，除了细胞死亡之外，还必须考虑其他因素。辐射不仅可能影响绝对淋巴细胞计数，还可能影响淋巴细胞的多样性和活性。综上所述，综述数据表明，淋巴细胞中辐射诱导的细胞死亡不太可能是辐射诱导淋巴细胞减少的唯一因素。
