Glioblastoma (GBM) is characterized by profound immunosuppression and poor response to immunotherapy. Sex biased incidence and outcomes suggest that immune programs may be differentially regulated in males and females, but the molecular substrates of this divergence remain incompletely defined. TACSTD2 (TROP2), an epithelial lineage marker and therapeutic target in multiple solid tumors, is normally silent in the brain yet becomes aberrantly reactivated in a subset of GBM via promoter CpG hypomethylation with sex modulated prognostic effects. The immune context of TACSTD2 reactivation in GBM is unknown. 
Here, we used publicly available deconvolution tools to characterize the association between TACSTD2 expression and tumor infiltrating immune cells in TCGA GBM and to place TACSTD2 within broader biological pathways through co expression and enrichment analysis. Immune infiltration was estimated using TIMER3 across multiple algorithms (including CIBERSORT and TME), and TACSTD2 correlated genes were analyzed with Enrichr (KEGG 2021 Human, MSigDB Hallmark 2020).
TIMER3 demonstrated modest but statistically significant positive correlations between TACSTD2 expression and CD4+ T cell memory estimates in GBM (CIBERSORT CD4+ memory resting: rho≈0.26, p≈2×10-3; T cell CD4+ CONSENSUS_TME: rho≈0.24, p≈4.5×10-3), with effect sizes comparable to those reported for established immune modulatory genes in deconvolution based GBM analyses. These correlations are moderate in magnitude and are interpreted as a correlative trend rather than a strong biomarker relationship. No strong negative correlation with global CD8+ T cell infiltration was observed, indicating that TACSTD2 reactivation does not simply mark a CD8 excluded or immune cold phenotype.
Pathway enrichment of TACSTD2 correlated genes (top 100, r>0.49) revealed dominant estrogen signaling, estrogen response, and apical junction signatures, alongside enrichment for ECM receptor interaction, focal adhesion and cell adhesion molecules, with minimal overlap with canonical immune checkpoint pathways. These findings support a model in which TACSTD2 marks a hormone tuned epithelial junction program that co varies with relative enrichment of CD4+ memory T cell infiltration, rather than functioning as a direct T cell intrinsic immune checkpoint. This purely computational study provides hypothesis generating, correlative evidence linking sex modulated TACSTD2 reactivation, epithelial hormone programs, and adaptive immune context in GBM, and it motivates future single cell, spatial, and functional studies to define causality and therapeutic relevance.

Glioblastoma, TACSTD2, TROP2, Immune infiltration, CD4+ memory T cells, Estrogen signaling, Epithelial programs