TGFβ1 and SMAD3 Expression Are Associated With Survival After the Immune Checkpoint Inhibitor Therapy for Small Cell Lung Cancer.

Cancer reports (Hoboken, N.J.) 2025

Seto Z, Inomata M, Noguchi A, Kado T, Murayama N, Takata N, Tokui K, Okazawa S, Imanishi S, Miwa T, Hayashi R, Hirabayashi K, Tobe K

Abstract

BACKGROUND: Tumor immunity is involved in the progression of malignant tumors. However, there are few reports on the relationship between the immunological environment and the efficacy of immune checkpoint inhibitors in small cell lung cancer (SCLC). We analyzed the relationship between tumor-infiltrating immune cells and protein expression and survival in patients with SCLC treated with combined therapy with immune checkpoint inhibitors plus chemotherapy. METHODS: Patients with SCLC who received combined therapy with immune checkpoint inhibitors plus chemotherapy between 2019 and 2023 were enrolled. Immune cell infiltration levels, including CD4, CD8, FOXP3, CD163-positive cells and expression levels of TGFβ1 and SMAD3 proteins in tumor tissue were evaluated by immunohistochemistry. Progression-free survival (PFS) and overall survival (OS) were evaluated as endpoints. RESULTS: Data from 22 patients were analyzed. The high CD4-positive T lymphocyte (p = 0.008, log-rank test) and the high CD8-positive T lymphocyte infiltration group (p = 0.031, log-rank test) showed statistically significantly longer OS than the low infiltration group. On the other hand, the low TGFβ1 expression group showed significantly longer PFS (p = 0.026, log-rank test) and the low SMAD3 expression group showed significantly longer OS (p = 0.042, log-rank test) than the high expression group. CONCLUSION: In conclusion, it is suggested that infiltration of T lymphocytes and expression of TGFβ1 and SMAD3 may be related to the efficacy of the combined therapy with immune checkpoint inhibitors plus chemotherapy in patients with SCLC.

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