Relationship and prognostic significance of IL-33, PD-1/PD-L1, and tertiary lymphoid structures in cervical cancer.

Abstract

IL-33, an epithelial-derived cytokine, functions as an alarmin for the immune system in the tumor microenvironment (TME). However, the expression and role of IL-33 on cervical cancer remain unclear. The aim of this study was to investigate the expression of IL-33 and its relationship with clinicopathologic features, tertiary lymphoid structures (TLS), and programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) immune checkpoints by immunohistochemistry in 93 cervical cancer patient specimens. Down-regulation of IL-33 expression was observed in tumor tissues compared with adjacent tissues. More importantly, IL-33 was detected in the cytoplasm of tumor fraction. IL-33 expression in tumor cytoplasm was associated with tumor size and the invasive depth of tumors (p < 0.05). Meanwhile, IL-33 expression in tumor cytoplasm was positively correlated with infiltration of CD3+ T cells, CD8+ T cells, and PD-L1 expression in tumor tissues (p < 0.05). The number of TLS strongly correlated with the depth of tumor invasion, preoperative chemotherapy, human papillomavirus infection, and high level of PD-1 (p < 0.05). However, there was no significant relationship between IL-33 and TLS. Kaplan-Meier survival curves showed that the formation of TLS was associated with a better prognosis (p = 0.008). In multivariable Cox regression modeling, high expression of PD-L1 in tumor tissues was correlated with poor prognosis (HR = 0.128; 95% CI: 0.026-0.646; p = 0.013), whereas the high expression of IL-33 in tumor tissues was associated with better prognosis (HR = 5.097; 95% CI:1.050-24.755; p = 0.043). These results indicate that IL-33, TLS, and PD-L1 are potentially valuable prognostic predictor for cervical cancer. IL-33 has potential for combination with PD-L1-related antitumor therapy.

• Authors: Ying Zhang, Jing Li, Fan Yang, Xiying Zhang, Xiubao Ren, Feng Wei
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 112 Issue 6 Pg. 1591-1603 (12 2022) ISSN: 1938-3673 [Electronic] United States
• PMID: 35501298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 Society for Leukocyte Biology.

Chemical References

• B7-H1 Antigen
• Programmed Cell Death 1 Receptor
• Interleukin-33

Topics

• Female
• Humans
• B7-H1 Antigen (metabolism)
• Prognosis
• Uterine Cervical Neoplasms (pathology)
• Programmed Cell Death 1 Receptor
• Tertiary Lymphoid Structures
• CD8-Positive T-Lymphocytes (metabolism)
• Interleukin-33
• Lymphocytes, Tumor-Infiltrating
• Tumor Microenvironment