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INTRODUCTION

CD8T cell tolerance plays an important role in tumor escape. Recent studies have shown that CD45 erythroid progenitor cells (CD45EPCs) generated through splenic extramedullary erythropoiesis suppress tumor immunity. However, the mechanism underlying how CD45EPCs mediate CD8T cell tolerance remains incompletely understood and requires further research.

METHODS

In this study, the antigen-processing abilities of CD45EPCs was verified through both in vitro and in vivo experiments. We have used the method of co-culture in vitro and adoptive transfer experiments in vivo to explore the effects of CD45EPCs on CD8T cell tolerance. RNA-sequencing analysis and blocking experiments were used to evaluate the role of ROS in the CD45EPC mediated tolerance of CD8T cells. Finally, we incorporated uric acid into the adoptive transfer experiments to rescue the CD45EPC mediated tumor-promoting effect.

RESULTS AND DISCUSSION

We found that CD45EPCs take up soluble proteins, present antigenic epitopes on their surface, and induce antigen-specific CD8T cell anergy. In addition, we found that CD45EPC directly nitrates tyrosine within the TCR/CD8 complex via the production of reactive oxygen species and peroxynitrite, preventing CD8 T cells from responding to their specific peptide antigens. Furthermore, uric acid treatment effectively abolished the immunosuppressive effects of CD45EPCs during CD8T cell adoptive transfer, thereby enhancing the anti-tumor efficacy. These results demonstrated that CD8T cell tolerance in tumor-bearing mice is induced by CD45EPCs. The results of this study have direct implications for tumor immunotherapy.

INTRODUCTION

METHODS

RESULTS AND DISCUSSION

简介

CD8T 细胞耐受在肿瘤逃逸中起着重要作用。最近的研究表明，通过脾脏髓外红细胞生成产生的 CD45 红细胞祖细胞（CD45EPC）抑制肿瘤免疫。然而，CD45EPC 介导 CD8T 细胞耐受的机制尚不完全清楚，需要进一步研究。

方法

在这项研究中，通过体外和体内实验验证了 CD45EPC 的抗原处理能力。我们使用体外共培养和体内过继转移实验的方法来探讨 CD45EPC 对 CD8T 细胞耐受的影响。RNA 测序分析和阻断实验用于评估 ROS 在 CD45EPC 介导的 CD8T 细胞耐受中的作用。最后，我们将尿酸纳入过继转移实验中，以挽救 CD45EPC 介导的促进肿瘤的作用。

结果与讨论

我们发现 CD45EPC 摄取可溶性蛋白，在其表面呈现抗原表位，并诱导抗原特异性 CD8T 细胞失能。此外，我们发现 CD45EPC 通过产生活性氧和过氧亚硝酸盐直接将酪氨酸硝化到 TCR/CD8 复合物中，从而阻止 CD8T 细胞对其特异性肽抗原产生反应。此外，尿酸处理可有效消除 CD8T 细胞过继转移过程中 CD45EPC 的免疫抑制作用，从而增强抗肿瘤疗效。这些结果表明，肿瘤荷瘤小鼠中的 CD8T 细胞耐受是由 CD45EPC 诱导的。本研究的结果对肿瘤免疫治疗具有直接意义。