宿主预处理的不同方法如何影响过继转移的抗肿瘤 T 辅助细胞的功效尚不清楚。具有识别酪氨酸酶相关肽 (TRP)-1 黑色素瘤抗原的转基因 T 细胞受体的 CD4 T 细胞被极化到 T 辅助细胞 17 ( Th17) 表型，然后转移到经过全身照射或化疗预处理的黑色素瘤小鼠体内。我们发现，用非清髓性剂量的全身照射（TBI 5 Gy）预处理小鼠比使用同等剂量的非清髓性照射更有效。 -清髓化疗（环磷酰胺（CTX）200mg/kg）增强抗肿瘤TRP-1 Th17细胞的治疗活性。经过 TBI 预处理后，抗肿瘤 Th17 细胞移植效果更好，并且使所有动物中已形成的大型黑色素瘤消退。相反，当用 CTX 预处理并注入抗黑色素瘤 Th17 细胞时，只有一半的小鼠能够长期存活。在接受 TBI 或 CTX 预处理的动物中检测到由输注的 Th17 细胞产生的白细胞介素 (IL)-17 和干扰素-γ。有趣的是，Th17 治疗后，与 CTX 相比，用 TBI 预处理的小鼠血清中炎症细胞因子（粒细胞集落刺激因子、IL-6、单核细胞趋化蛋白 1、IL-5 和角质形成细胞趋化剂）显着升高。在 CTX (200mg/kg) 中添加氟达拉滨 (FLU，200mg/kg) 可改善 TBI 介导的抗肿瘤反应，而单独使用 FLU 联合 Th17 治疗则无效。我们的结果首次表明， Th17 治疗产生的抗肿瘤反应、持久性和细胞因子谱受到宿主预处理的特定方案的影响。这项工作对于理解通过过继性细胞疗法促进长期反应的机制非常重要，特别是基于 CD4 的 T 细胞疗法现在在临床中出现。© 作者（或其雇主）2024。重新- CC BY-NC 允许使用。禁止商业再利用。请参阅权利和权限。由英国医学杂志出版。

How distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.CD4+ T cells with a transgenic T-cell receptor that recognize tyrosinase-related peptide (TRP)-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (cyclophosphamide (CTX) of 200 mg/kg) at augmenting therapeutic activity of antitumor TRP-1 Th17 cells. Antitumor Th17 cells engrafted better following preconditioning with TBI and regressed large established melanoma in all animals. Conversely, only half of mice survived long-term when preconditioned with CTX and infused with anti-melanoma Th17 cells. Interleukin (IL)-17 and interferon-γ, produced by the infused Th17 cells, were detected in animals given either TBI or CTX preconditioning. Interestingly, inflammatory cytokines (granulocyte colony stimulating factor, IL-6, monocyte chemoattractant protein-1, IL-5, and keratinocyte chemoattractant) were significantly elevated in the serum of mice preconditioned with TBI versus CTX after Th17 therapy. The addition of fludarabine (FLU, 200 mg/kg) to CTX (200 mg/kg) improved the antitumor response to the same degree mediated by TBI, whereas FLU alone with Th17 therapy was ineffective.Our results indicate, for the first time, that the antitumor response, persistence, and cytokine profiles resulting from Th17 therapy are impacted by the specific regimen of host preconditioning. This work is important for understanding mechanisms that promote long-lived responses by adoptive cellular therapy, particularly as CD4+ based T-cell therapies are now emerging in the clinic.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.