NLRP3 inflammasome upregulates PD-L1 expression and contributes to immune suppression in lymphoma #MMPMID33091534
Lu F; Zhao Y; Pang Y; Ji M; Sun Y; Wang H; Zou J; Wang Y; Li G; Sun T; Li J; Ma D; Ye J; Ji C
Cancer Lett 2021[Jan]; 497 (?): 178-189 PMID33091534show ga
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.
|*Gene Expression Regulation, Neoplastic[MESH]
|Adult[MESH]
|Aged[MESH]
|Aged, 80 and over[MESH]
|Animals[MESH]
|Apoptosis[MESH]
|B7-H1 Antigen/genetics/*metabolism[MESH]
|Biomarkers, Tumor/genetics/*metabolism[MESH]
|Cell Proliferation[MESH]
|Female[MESH]
|Humans[MESH]
|Inflammasomes/*immunology[MESH]
|Lymphoma, Large B-Cell, Diffuse/*immunology/metabolism/*pathology[MESH]
Cancer+Lett 2021 ; 497 (?): 178-189
