Mobile website
Basic Research
Blocking HMGB1 mitigates lung injury in mice with lung cancer xenografts following combined radiotherapy and PD-1 inhibitor treatment
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
[Abstract] Objective: To investigate the effect of high mobility group box-1 protein (HMGB1) neutralizing antibodies on radiationinduced lung injury in transplanted tumor-bearing mice. Methods: Twenty-five male C57BL/6 mice were randomly divided into five groups: control group, PD-1 inhibitor group, radiotherapy group, radiotherapy + PD-1 inhibitor group, and HMGB1 neutralizing antibody + PD-1 inhibitor + radiotherapy group, with five mice in each group. Subcutaneous transplantation of lung carcinoma LLC cells was performed on the right hind limb of each animal to establish the primary tumor, whilst subcutaneous transplantation of LLC cells on the left hind limb served as the secondary tumor. On day 28 of the experiment, animals were euthanized, and lung tissue and transplanted tumors were collected. Hematoxylin and eosin (H-E) staining and Masson's trichrome staining were performed to observe the pathological changes in the lung tissues of experimental mice. Immunohistochemistry (IHC) was used to detect the infiltration of CD4+ and CD8+ T lymphocytes in lung and transplanted tumor tissues. Enzyme-linked immunosorbent assay (ELISA) was used to examine the expression of TNF-α, TGF-β, and IL-6 in lung tissues. Results: Compared with the control and PD-1 inhibitor groups, the other three groups showed significantly reduced transplanted tumor volumes (P < 0.01 or P < 0.001), with HMGB1 neutralizing antibodies not further decreasing tumor volume. Similarly, compared with the control and PD-1 inhibitor groups, the inflammation scores and collagen volume fraction (CVF) in lung tissues were notably increased in the other three groups (P < 0.05, P < 0.01, P < 0.001, or P < 0.0001), and HMGB1 neutralizing antibodies partially inhibited the adverse effects of radiotherapy (P < 0.01 or P < 0.001). Compared to the control or PD-1 inhibitor groups, CD4+ T lymphocyte infiltration was significantly increased in the lung tissues of the other three groups, and HMGB1 neutralizing antibodies partially inhibited CD4+ T lymphocyte infiltration in lung tissue (P < 0.01). Moreover, in the transplanted tumor tissues, compared with the control or PD-1 inhibitor groups, the other three groups demonstrated significantly increased CD4+ and CD8+ T lymphocyte infiltration (all P < 0.001); however, HMGB1 neutralizing antibodies did not inhibit T cell infiltration in the transplanted tumor tissues. Compared with the control or PD-1 inhibitor groups, IL-6 expression in lung tissue was elevated and TGF-β expression was decreased in the other three groups (P < 0.05), and HMGB1 neutralizing antibodies had no significant effect on the expression of TNF-α, IL-6, or TGF-β in lung tissue. Conclusion: HMGB1 neutralizing antibodies may reduce the infiltration of inflammatory cells in the lungs, thereby alleviating lung inflammatory injury and fibrosis, without affecting the inhibition of transplanted tumor growth effects.
Keywords:
Project Supported:
Clc Number:
