Research on the functional role and molecular mechanism of IL-36γ mediating CD8⁺ T cells antitumor immune response

WU Ming-xing; CAO Zhen-dong; XU Wen-hui; ZHU Yi-min

doi:10.11659/jjssx.12E025072

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Research on the functional role and molecular mechanism of IL-36γ mediating CD8⁺ T cells antitumor immune response

Basic Research | 更新时间：2026-10-26

- Research on the functional role and molecular mechanism of IL-36γ mediating CD8⁺ T cells antitumor immune response
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 10, Pages: 873-878(2026)
- 作者机构：
  
  南京中医药大学第二附属医院/江苏省第二中医院呼吸科，江苏南京 210017
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.12E025072
  CLC： R730.3
- Received：15 December 2025，
  
  Published：25 October 2026
- 稿件说明：
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吴明星,曹振东,徐文慧等.IL-36γ介导CD8⁺ T细胞抗肿瘤免疫应答的作用及其分子机制研究[J].局解手术学杂志,2026,35(10):873-878.

WU Ming-xing,CAO Zhen-dong,XU Wen-hui,et al.Research on the functional role and molecular mechanism of IL-36γ mediating CD8⁺ T cells antitumor immune response[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(10):873-878.
吴明星,曹振东,徐文慧等.IL-36γ介导CD8⁺ T细胞抗肿瘤免疫应答的作用及其分子机制研究[J].局解手术学杂志,2026,35(10):873-878. DOI： 10.11659/jjssx.12E025072.

WU Ming-xing,CAO Zhen-dong,XU Wen-hui,et al.Research on the functional role and molecular mechanism of IL-36γ mediating CD8⁺ T cells antitumor immune response[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(10):873-878. DOI： 10.11659/jjssx.12E025072.

摘要

目的

探讨白细胞介素（IL）-36γ对CD8⁺ T细胞程序性死亡受体-1（PD-1）表达及抗肿瘤免疫应答的影响。

方法

采用BALB/c和C57BL/6小鼠分别建立CT26.WT结肠癌和B16黑色素瘤模型，每种模型设置vector组和IL-36γ组。比较第14天各组小鼠的肿瘤体积，并检测肿瘤浸润性CD8

T细胞中PD-1表达。体外分离CD8

T细胞并诱导获得Tc0、Tc1细胞，采用流式细胞术检测不同细胞因子及IL-36γ处理后CD8

T细胞中PD-1表达；同时比较IL-36γ对WT与T-bet⁻/⁻来源的CD8⁺ T细胞中PD-1表达的影响。

结果

CD8

T细胞经干扰素-γ(IFN-γ)和IL-2处理后PD-1平均荧光强度无显著变化（

0.05），经IL-12、转化生长因子-β(TGF-β)和IL-1β处理后PD-1平均荧光强度升高（

0.05），而经IL-18、IL-33、IL-36α、IL-36β及IL-36γ处理后PD-1平均荧光强度降低（

0.05），其中IL-36γ的抑制作用最显著。Tc0和Tc1细胞在IL-36γ处理24、36、48 h后的PD-1阳性细胞比例均低于相应Medium对照（

0.05）。经IL-36γ处理后，CT26.WT-IL-36γ组和B16-IL-36γ组小鼠的肿瘤体积均显著减小（

0.05），肿瘤浸润性CD8⁺ T细胞PD-1平均荧光强度显著降低（

0.05）。在WT来源CD8⁺ T细胞中，IL-36γ处理后PD-1平均荧光强度显著降低（

0.05）；而在T-bet⁻/⁻来源CD8⁺ T细胞中，IL-36γ与Medium处理后PD-1平均荧光强度差异无统计学意义（

0.05）。

结论

IL-36γ可降低CD8⁺ T细胞PD-1表达，并与小鼠肿瘤生长受抑及肿瘤浸润性CD8⁺ T细胞PD-1表达降低相关；T-bet可能参与IL-36γ对PD-1表达的调控，但其具体分子机制仍需进一步验证。

Abstract

Objective

To investigate the effects of interleukin （IL）-36γ on programmed death 1 （PD-1） expression in CD8

T cells and the antitumor immune responses.

Methods

BALB/c and C57BL/6 mice were used to establish CT26.WT colon carcinoma and B16 melanoma models

，respectively. For each tumor model，mice were assigned to a vector control group or an IL-36γ-overexpression group. The tumor volumes of mice in each group were compared on the 14th day， and the expression of PD-1 in tumor-infiltrating CD8

T cells was detected. CD8

T cells were isolated in vitro and induced to differentiate into Tc0 and Tc1 subsets. Flow cytometry was used to assess PD-1 expression following treatment with different cytokines or IL-36γ. The effects of IL-36γ on PD-1 expression in CD8

T cells derived from WT and T-bet⁻/⁻ mice were also compared.

Results

The mean fluorescence intensity of PD-1 in CD8

T cells showed no significant change after treatment with interferon -γ（IFN-γ） and IL-2 （

0.05）， while the mean fluorescence intensity of PD-1 increased after treatment with IL-12，transforming growth factor-β（TGF-β） and IL-1β （

0.05）. The mean fluorescence intensity of PD-1 decreased after treatment with IL-18，IL-33，IL-36α，IL-36β and IL-36γ （

0.05），among which the inhibitory effect of IL-36γ was the most significant.The proportions of PD-1 positive cells in Tc0 and Tc1 cells after treatment with IL-36γ for 24， 36， and 48 hours were all lower than those in the corresponding Medium control （

0.05）. After treatment with IL-36γ， the tumor volumes of mice in both CT26.WT-IL-36γ group and B16-IL-36γ group were significantly reduced （

0.05），and the mean fluorescence intensity of PD-1 in tumor-infiltrating CD8

T cells were significantly decreased （

0.05）. IL-36γ treatment significantly reduced the mean fluorescence intensity of PD-1 in WT-derived CD8

T cells，whereas no significant difference in the mean fluorescence intensity of PD-1 was observed in T-bet⁻/⁻-derived CD8

T cells which treated with Medium or IL-36γ.

Conclusion

IL-36γ can reduce

the expression of PD-1 in CD8

T cells and is associated with the inhibition of tumor growth in mice and the decrease of PD-1 expression in tumor-infiltrating CD8

T cells. T-bet may be involved in the regulation of PD-1 expression by IL-36γ， but its specific molecular mechanism still needs to be further verified.

关键词

Keywords

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