PD-1 and TIGIT Are Highly Co-Expressed on CD8(+) T Cells in AML Patient Bone Marrow.
PD-1 and TIGIT Are Highly Co-Expressed on CD8(+) T Cells in AML Patient Bone Marrow.
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PD-1 和 TIGIT 在 AML 患者骨髓中的 CD8( ) T 细胞上高度共表达
DOI：
10.3389/fonc.2021.686156
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发表时间：
2021
影响因子：
4.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Xu L;Liu L;Yao D;Zeng X;Zhang Y;Lai J;Zhong J;Zha X;Zheng R;Lu Y;Li M;Jin Z;Hebbar Subramanyam S;Chen S;Huang X;Li Y
尽管免疫检查点抑制剂（ICI）治疗多种癌症取得了巨大成功，但ICI在急性髓性白血病（AML）中的临床应用证据仍然不足。进一步探索骨髓（BM）环境、原发性白血病部位和外周血（PB）中免疫逃避的原因，以及了解T细胞如何受到AML诱导化疗或年龄的影响，可能有助于选择可能受益于ICI治疗的患者。在这项研究中，我们全面比较了两种研究最充分的IC蛋白PD-1和TIGIT在AML患者在初始诊断、完全缓解（CR）和化疗后复发难治性（R/R）疾病阶段的PB和BM T细胞中的分布。我们的研究结果显示PD-1在新生（DN）和R/R患者的PB和BM T细胞中普遍表达较高，而在CR患者中部分恢复。在DN和R/R患者的CD8+ T细胞的BM中，TIGIT的表达增加，但在CR中没有恢复。此外，根据年龄相关性分析，我们发现老年AML患者在PB和BM中PD-1和TIGIT单阳性CD8+ T细胞的比例更高，这表明老年患者的T细胞功能受损更大。此外，我们发现DN和R/R患者在BM中积累的PD-1+和TIGIT+ CD8+ T细胞的频率高于相应的PB，这表明白血病BM中更具免疫抑制性的微环境可能促进疾病进展。总之，我们的研究可能有助于指导联合使用抗pd -1和抗tigit抗体治疗老年AML患者，并为探索恢复免疫抑制BM微环境的策略铺平道路，以提高AML患者的生存率。
Despite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site, and peripheral blood (PB) and understanding how T cells are affected by AML induction chemotherapy or the influence of age may help to select patients who may benefit from ICI treatment. In this study, we comprehensively compared the distribution of PD-1 and TIGIT, two of the most well-studied IC proteins, in PB and BM T cells from AML patients at the stages of initial diagnosis, complete remission (CR), and relapse-refractory (R/R) disease after chemotherapy. Our results show that PD-1 was generally expressed higher in PB and BM T cells from de novo (DN) and R/R patients, while it was partially recovered in CR patients. The expression of TIGIT was increased in the BM of CD8+ T cells from DN and R/R patients, but it did not recover with CR. In addition, according to age correlation analysis, we found that elderly AML patients possess an even higher percentage of PD-1 and TIGIT single-positive CD8+ T cells in PB and BM, which indicate greater impairment of T cell function in elderly patients. In addition, we found that both DN and R/R patients accumulate a higher frequency of PD-1+ and TIGIT+ CD8+ T cells in BM than in corresponding PB, indicating that a more immunosuppressive microenvironment in leukemia BM may promote disease progression. Collectively, our study may help guide the combined use of anti-PD-1 and anti-TIGIT antibodies for treating elderly AML patients and pave the way for the exploration of strategies for reviving the immunosuppressive BM microenvironment to improve the survival of AML patients.
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影响因子：
10.9
作者：
Gong J;Chehrazi-Raffle A;Reddi S;Salgia R
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发表时间：
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期刊：
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影响因子：
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影响因子：
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