Earle A Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, Oregon, United States of America.
PLoS One. 2013 Jul 25;8(7):e69527. doi: 10.1371/journal.pone.0069527. Print 2013.
Expansion of myeloid-lineage leukocytes in tumor-bearing mice has been proposed as a cause of systemic immunosuppression. We demonstrate that radiation therapy of tumors leads to a decline in myeloid cell numbers in the blood and a decrease in spleen size. The frequency of myeloid cells does not decline to the level seen in tumor-free mice: we demonstrate that metastatic disease can prevent myeloid cell numbers from returning to baseline, and that tumor recurrence from residual disease correlates with re-expansion of myeloid lineage cells. Radiation therapy results in increased proliferation of T cells in the spleen and while T cell responses to foreign antigens are not altered by tumor burden or myeloid cell expansion, responses to tumor-associated antigens are increased after radiation therapy. These data demonstrate that myeloid cell numbers are directly linked to primary tumor burden, that this population contracts following radiation therapy, and that radiation therapy may open a therapeutic window for immunotherapy of residual disease.
肿瘤荷瘤小鼠骨髓谱系白细胞的扩增被认为是全身免疫抑制的原因。我们证明,肿瘤的放射治疗导致血液中骨髓细胞数量减少,脾脏缩小。骨髓细胞的频率不会下降到无肿瘤小鼠的水平:我们证明转移性疾病可以阻止骨髓细胞数量恢复到基线水平,而残留疾病的肿瘤复发与骨髓谱系细胞的重新扩增相关。放射治疗导致脾脏中 T 细胞增殖增加,尽管肿瘤负担或骨髓细胞扩增不会改变 T 细胞对外来抗原的反应,但对肿瘤相关抗原的反应在放射治疗后增加。这些数据表明,骨髓细胞数量与原发性肿瘤负担直接相关,该群体在放射治疗后收缩,放射治疗可能为残留疾病的免疫治疗开辟一个治疗窗口。