Gyógyszerészet, farmakogenomika, gyógyszerkutatás és tervezés, gyógyszeres kezelés
Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival
outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression
across cancers, but its role in SCLC has not yet been elucidated. This research explores
the expression patterns and prognostic significance of CD70 and CD27 in early-stage
SCLC.In this retrospective study, we analyzed 190 surgically resected SCLC tumor samples
using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70
RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining.
Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier
survival analysis and multivariate Cox regression were used to assess the prognostic
impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).CD70 was
expressed in 46% of tumors, primarily within tumor nests, with lower expression in
stromal areas. High CD70 expression correlated with significantly decreased OS (p
= 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune
cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not
show a significant association with OS (p = 0.582). Importantly, high CD27 expression
was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and
CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules
exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 +
B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly
improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune
responses in SCLC prognosis.CD70, B-cell density and the presence of TLSs, but not
CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC,
suggesting its potential as a therapeutic target.