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Archive > Volume 32 Issue 8 > 2025,32(8):839-846. DOI:10.3872/j.issn.1007-385X.2025.08.007 Prev Next
Clinical Research
Interleukin-37 suppresses the cytotoxicity of CD8+ T cells in the peripheral blood and tumor microenvironments in breast cancer patients
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Abstract:
[Abstract] Objective: To investigate the effects of changes in interleukin-37 (IL-37) expression on CD8+ T cell vitality in patients with breast cancers. Methods: Forty-six patients with breast cancers, twenty-four patients with benign breast tumors, and twenty controls enrolled at the First Affiliated Hospital of Xinxiang Medical University between July 2020 and September 2022 were included in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells (PBMC) were isolated. Tumor tissues and para-cancerous tissues were collected from breast cancer patients who received surgical treatment. Tumor infiltrating lymphocytes (TILs) were isolated and CD8+ T cells purified. IL-37 and the expressions of soluble single immunoglobin IL-1 receptor-related (SIGIRR) proteins were detected by enzyme-linked immunosorbent assay (ELISA). IL-37 mRNA in the tissue was measured by real time PCR. IL-18 receptor α chain (IL-18Rα) and SIGIRR expression in CD8+ T cells were measured by flow cytometry. Purified CD8+ T cells were stimulated with exogenous IL-37, and were co-cultured with breast cancer cell line MCF-7. The percentage of target cell death was calculated by measuring the level of lactate dehydrogenase. Perforin, granzyme B, interferon-γ（IFN-γ）, and the level of tumor necrosis factor-α (TNF-α) in the supernatants was detected by ELISA. Results: Plasma IL-37 level was significantly elevated in patients with breast cancer compared with that in patients with benign breast tumors ([554.17 ± 96.63] vs [499.52 ± 78.66] pg/mL, P = 0.020) and that in the controls ([483.97 ± 47.23] pg/mL, P = 0.003). The expression of IL-37 mRNA in the tumor tissues was higher than that in the para-cancerous tissues in patients with breast cancer ([1.88 ± 0.21] vs [1.00 ± 0.53] pg/mL, P < 0.001). There were no statistically significant differences of peripheral IL-18Rα+CD8+ cell percentage, SIGIRR+ CD8+ cell percentage, or the level of soluble SIGIRR among patients with breast cancer, patients with benign breast tumors, and the controls (P > 0.05). There were also no statistically significant differences of the percentages of IL-18Rα+ or SIGIRR+ expression in CD8+ TIL cells between the tumor tissues and the para-cancerous tissues (P > 0.05). The percentage of CD8+ T cell-induced target cell death, and the levels of IFN-γ and TNF-α in the supernatants in both direct contact and indirect contact co-culture systems were reduced with IL-37 stimulation compared with those without IL-37 stimulation(P < 0.05). In direct contact co-culture system, the levels of perforin and granzyme B in the supernatants were down-regulated in response to IL-37 stimulation compared with those without stimulation (P < 0.001). However, in indirect contact co-culture system there were no significant differences in the levels of perforin or granzyme B in the supernatants with or without IL-37 stimulation (P > 0.05). Conclusion: Elevated IL-37 level might take part in the induction of CD8+ T cell exhaustion in peripheral blood and tumor microenvironments in breast cancer patients.
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