Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Department of Medicine, Veterans Administration Healthcare System, Palo Alto, California, USA.
JCI Insight. 2020 Feb 27;5(4):134569. doi: 10.1172/jci.insight.134569.
Adjuvant chemotherapy in breast cancer patients causes immune cell depletion at an age when the regenerative capacity is compromised. Successful regeneration requires the recovery of both quantity and quality of immune cell subsets. Although immune cell numbers rebound within a year after treatment, it is unclear whether overall compositional diversity is recovered. We investigated the regeneration of immune cell complexity by comparing peripheral blood mononuclear cells from breast cancer patients ranging from 1-5 years after chemotherapy with those of age-matched healthy controls using mass cytometry and T cell receptor sequencing. These data reveal universal changes in patients' CD4+ T cells that persisted for years and consisted of expansion of Th17-like CD4 memory populations with incomplete recovery of CD4+ naive T cells. Conversely, CD8+ T cells fully recovered within a year. Mechanisms of T cell regeneration, however, were unbiased, as CD4+ and CD8+ T cell receptor diversity remained high. Likewise, terminal differentiated effector memory cells were not expanded, indicating that regeneration was not driven by recognition of latent viruses. These data suggest that, while CD8+ T cell immunity is successfully regenerated, the CD4 compartment may be irreversibly affected. Moreover, the bias of CD4 memory toward inflammatory effector cells may impact responses to vaccination and infection.
辅助化疗会导致乳腺癌患者的免疫细胞耗竭，而此时的再生能力已经受损。成功的再生需要恢复免疫细胞亚群的数量和质量。尽管在治疗后一年内免疫细胞数量会反弹，但尚不清楚整体组成多样性是否得到恢复。我们使用质谱流式细胞术和 T 细胞受体测序，比较了化疗后 1-5 年的乳腺癌患者和年龄匹配的健康对照者的外周血单核细胞，以此来研究免疫细胞复杂性的再生。这些数据揭示了患者 CD4+T 细胞的普遍变化，这些变化持续多年，包括 Th17 样 CD4 记忆细胞群的扩增，而 CD4+幼稚 T 细胞未能完全恢复。相反，CD8+T 细胞在一年内完全恢复。然而，T 细胞再生的机制是无偏见的，因为 CD4+和 CD8+T 细胞受体多样性仍然很高。同样，终末分化的效应记忆细胞也没有扩增，表明再生不是由潜伏病毒的识别所驱动的。这些数据表明，虽然 CD8+T 细胞免疫成功再生，但 CD4 细胞群可能受到不可逆转的影响。此外，CD4 记忆细胞向炎症效应细胞的偏向可能会影响对疫苗和感染的反应。
