Trop-2 expression and the tumor microenvironment in gastric cancer.

446 Background: Trophoblast Cell Surface Antigen 2 (TROP2) is a transmembrane glycoprotein that has emerged as a promising therapeutic target due to its frequent overexpression in diverse epithelial malignancies, including gastric cancer. Beyond its role in promoting tumor cell proliferation and survival, TROP2 has been implicated in modulating tumor-immune interactions, raising interest in its potential as a marker for immune-based therapies. However, the relationship between TROP2 expression and the cellular composition of the tumor microenvironment (TME) in gastric cancer remains insufficiently characterized. Methods: To systematically investigate the influence of TROP2 on the gastric cancer TME, we analyzed 8 publicly available cohorts/trials encompassing 1,351 clinically annotated gastric cancer samples with whole transcriptome sequencing data available. Within each cohort, TROP2 ( TACSTD2 ) expression was quantified and stratified into high and low groups using the median of log-transformed TPM values per cohort. We employed the xCell immune deconvolution algorithm to estimate the relative enrichment of immune and stromal cell populations, enabling pan-cohort comparisons of TME composition according to TROP2 status. Results: Across cohorts, we did not observe any immune or stromal cell populations that were consistently enriched in TROP2-high gastric cancers. However, TROP2-high tumors exhibited a reproducible and statistically significant reduction in several key components of the tumor microenvironment, most notably CD8 + cytotoxic T cells, cancer-associated fibroblasts, hematopoietic stem cells, and myeloid dendritic cells. These depletions were observed with relative consistency across the majority of datasets (at least 5 out of 8 cohorts with p