| Title: |
Immune Microenvironment of Non-Small Cell Lung Cancer Bone Metastases is "Cold" and Remodeled by Anti-PD-L1 Therapy in a Syngeneic Murine Model. |
| Authors: |
Massy, Emmanuel; Point, Mathieu; Bouazza, Lamia; Brevet, Marie; Girard, Nicolas; Pialat, Jean Baptiste; Clézardin, Philippe; Bonnelye, Edith; Confavreux, Cyrille |
| Source: |
JBMR Plus; 2026 Supplement, Vol. 10, p25-26, 2p |
| Subject Terms: |
BONE metastasis; PROGRAMMED death-ligand 1; TUMOR microenvironment; NON-small-cell lung carcinoma; LABORATORY mice; T-cell exhaustion; IMMUNE checkpoint inhibitors; MACROPHAGE activation |
| Abstract: |
Introduction: Non-small cell lung cancer (NSCLC) is highly incident, and 40% of patients develop bone metastases (BM), which severely impact prognosis. Immune checkpoint inhibitors (ICIs) show reduced efficacy in patients with bone metastases, suggesting a unique immune microenvironment in the bone. Purpose: We aimed to characterize the immunological differences between NSCLC primary tumors (PT) and BM, and to investigate the effects of anti-PD-L1 therapy on the immune cell populations within the bone microenvironment in vivo. Methods: In a prospective human cohort (POUMOS, ethical protocol n°11-480), NSCLC PT and BM tissues were analyzed using multiplex immunohistochemistry to characterize CD8+ T cells and CD4+ subsets. In parallel, a syngeneic murine model was established using CMT167 cells to induce orthotopic BM. Mice were treated by anti-PD-L1 or control antibody. Immune responses were assessed by flow cytometry and bone metastasis by microCT. Results: IHC analysis showed that NSCLC BM were "cold", characterized by a lower infiltration of CD8+ effector T cells (35.1±28.2 in PT vs 1.3±1.6 cells/mm² in BM, p=0.0006) and CD4+ Th1 lymphocytes (24.57±32.63 in PT vs. 0.37±0.50 cells/mm² in BM, p=0.03). Macrophages exhibited a predominant M2 phenotype in BM with M1/M2 ratio 4.42±5.75 for PT vs. 0.21±0.27 in BM, p=0.03. Moreover, in vivo anti-PD-L1 treatment increased the proportion of CD4+ (1.7±0.3 fold change, p0.05) in the bone microenvironment. MicroCT analysis revealed no difference in bone microarchitecture between anti-PD-L1 and control groups. Conclusion: NSCLC bone metastases display a distinct, immunosuppressive microenvironment, notably lacking CD8 effectors and Th1 cells. Anti-PD-L1 therapy successfully induces an increase in effector T lymphocytes in the bone microenvironment in vivo, though this was not associated with changes in bone destruction. This suggests that ICIs effectively modulate local immunity, but their impact on bone structure may require combined therapeutic approaches. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |