2. Academic Validation
  3. NLRP3 inflammasome upregulates PD-L1 expression and contributes to immune suppression in lymphoma

NLRP3 inflammasome upregulates PD-L1 expression and contributes to immune suppression in lymphoma

  • Cancer Lett. 2021 Jan 28;497:178-189. doi: 10.1016/j.canlet.2020.10.024.
Fei Lu 1,  Yanan Zhao 1,  Yihua Pang 1,  Min Ji 1,  Yanping Sun 1,  Hongchun Wang 2,  Jie Zou 3,  Yan Wang 4,  Guosheng Li 1,  Tao Sun 1,  Jingxin Li 5,  Daoxin Ma 1,  Jingjing Ye 6,  Chunyan Ji 7
Affiliations

Affiliations

  • 1 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
  • 2 Department of Laboratory Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
  • 3 Department of Geriatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
  • 4 Department of Hematology, Taian City Central Hospital, Taian, Shandong, 271000, PR China.
  • 5 Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
  • 6 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address: jingjing_ye@163.com.
  • 7 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address: jichunyan@sdu.edu.cn.
PMID: 33091534 DOI: 10.1016/j.canlet.2020.10.024
Abstract

The NLRP3 inflammasome plays a pro-tumorigenic role in various malignancies. However, its potential role in lymphomagenesis remains unclear. In this study, we identified an immunosuppressive state in patients with diffuse large B cell lymphoma (DLBCL), which was characterized by markedly elevated interleukin (IL)-18 levels in lymphoma tissues and positive correlation with programmed death ligand 1 (PD-L1) expression. Furthermore, NLRP3 inflammasome activation in DLBCL cell lines upregulated PD-L1 and reduced the proportion of cytotoxic T cells. NLRP3 inflammasome blockade in vivo suppressed lymphoma growth and ameliorated anti-tumor immunity by downregulating PD-L1 in the tumor microenvironment and decreasing the proportion of PD-1/TIM-3-expressing T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Further in vivo studies revealed IL-18 as the main effector cytokine involved in the negative regulation of anti-lymphoma immunity. Interestingly, NLRP3 blockers combined with anti-PD-L1 treatment exerted antagonistic effects during lymphoma therapy. Altogether, our findings indicate that NLRP3 inflammasome promotes immunosuppression by modulating PD-L1 and immune cells. Accordingly, this study highlights the prognostic and therapeutic values of the NLRP3 inflammasome in lymphoma.

Keywords

Diffuse large B cell lymphoma; Immune checkpoints; Immunosuppression; Interleukin-18; NLRP3.

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