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南昌大学发表最新Nature子刊论文

  • 2026-02-14 09:33:55
南昌大学发表最新Nature子刊论文

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组蛋白乳酰化上调CXCL1表达促进胰腺癌中性粒细胞募集与免疫逃逸
论文信息
南昌大学第一附属医院张呈生教授团队提出，有氧糖酵解产生的乳酸通过诱导组蛋白H3第18位赖氨酸乳酰化（H3K18la）上调趋化因子CXCL1的表达，进而招募中性粒细胞并促进胰腺癌的免疫逃逸。该团队设计了整合生物信息学分析与实验验证的研究方案，首先证实了乳酸介导的H3K18la修饰对CXCL1的转录激活作用，继而鉴定出p300/CBP相关因子（PCAF）作为关键的组蛋白乳酰基转移酶介导这一过程。在此基础上，团队进一步设计了联合治疗策略，通过使用PCAF抑制剂bromosporine与抗PD-1抗体联用，在胰腺癌皮下及原位模型中证实了协同抗肿瘤效应，为胰腺癌的免疫治疗提供了新思路。
研究成果于2026年2月9日以题为“Histone lactylation increases CXCL1 expression for neutrophil infiltration and immune escape in pancreatic cancer”发表在《Nature Communications》上。
图文解读
图1：糖酵解招募中性粒细胞，促进胰腺癌进展。图1通过生物信息学分析和体内功能实验，揭示了糖酵解在胰腺癌中的关键免疫调节作用。研究发现，高糖酵解水平与肿瘤内中性粒细胞浸润增加、CD8+ T细胞浸润减少及患者不良预后显著相关。利用抑制剂或基因敲低手段抑制糖酵解，可有效减少肿瘤内中性粒细胞，并增加功能性CD8+ T细胞的浸润，从而抑制肿瘤生长。功能学实验进一步证实，糖酵解是通过驱动中性粒细胞浸润来介导免疫抑制、促进胰腺癌进展的。
图2：糖酵解通过促进Cxcl1的表达来增强中性粒细胞的浸润。图2通过转录组筛选、体外及体内功能实验，系统鉴定了介导糖酵解招募中性粒细胞的关键趋化因子CXCL1。研究发现，抑制肿瘤细胞糖酵解可显著降低CXCL1的转录与分泌。体外趋化实验证实，CXCL1的下调直接导致其对中性粒细胞招募能力的减弱。在动物模型中，恢复CXCL1表达能有效逆转因糖酵解抑制所导致的肿瘤生长受限和中性粒细胞浸润减少。因此，糖酵解是通过上调CXCL1表达来驱动中性粒细胞向肿瘤微环境募集的核心机制。
文章小结
本研究揭示了胰腺癌中有氧糖酵解产物乳酸通过表观遗传调控驱动免疫逃逸的新机制。研究证实，乳酸诱导的组蛋白H3K18乳酰化（H3K18la）由乳酰基转移酶PCAF催化，直接激活趋化因子CXCL1的转录表达，从而招募中性粒细胞浸润肿瘤微环境并介导免疫抑制。基于这一机制，团队进一步设计了PCAF抑制剂bromosporine与抗PD-1抗体的联合治疗策略，在胰腺癌原位模型中证实该联合方案可有效减少中性粒细胞浸润、增强CD8⁺ T细胞抗肿瘤免疫应答，并显著延长荷瘤小鼠生存期。该研究不仅阐明了乳酸-PCAF-H3K18la-CXCL1信号轴在胰腺癌免疫逃逸中的核心作用，还为胰腺癌免疫治疗提供了基于表观遗传调控的新型联合治疗策略。
文献来源
Zhang, P., Ma, J., Wan, Y. et al. Histone lactylation increases CXCL1 expression for neutrophil infiltration and immune escape in pancreatic cancer. Nat Commun (2026). 
DOI：https://doi.org/10.1038/s41467-026-69311-5

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  1. CONNECT:[ UseTime:0.000675s ] mysql:host=127.0.0.1;port=3306;dbname=aa460;charset=utf8mb4
  2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.000961s ]
  3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.000299s ]
  4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.000277s ]
  5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.000785s ]
  6. SELECT * FROM `set` [ RunTime:0.000224s ]
  7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.000652s ]
  8. SELECT * FROM `article` WHERE `id` = 473805 LIMIT 1 [ RunTime:0.004771s ]
  9. UPDATE `article` SET `lasttime` = 1771039070 WHERE `id` = 473805 [ RunTime:0.000825s ]
  10. SELECT * FROM `fenlei` WHERE `id` = 64 LIMIT 1 [ RunTime:0.000265s ]
  11. SELECT * FROM `article` WHERE `id` < 473805 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.000890s ]
  12. SELECT * FROM `article` WHERE `id` > 473805 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.001151s ]
  13. SELECT * FROM `article` WHERE `id` < 473805 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.013502s ]
  14. SELECT * FROM `article` WHERE `id` < 473805 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.008321s ]
  15. SELECT * FROM `article` WHERE `id` < 473805 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.012911s ]
0.112544s