Biology subjects

Jamaspishvilli, T.

Publications and source records attributed to Jamaspishvilli, T..

3 recordsLinked to original sources

bioRxiv2025

Towards interpretable molecular and spatial analysis of the tumor microenvironment from digital histopathology images with HistoTME-v2

The tumor microenvironment (TME) is a critical focus for biomarker discovery and therapeutic targeting in cancer. However, widespread clinical adoption of TME profiling is hindered by the high cost and technical complexity of current platforms such as spatial transcriptomics and proteomics. Artificial Intelligence (AI)-based analysis of the TME from routine Hematoxylin & Eosin (H&E)-stained pathology slides presents a promising alternative. Yet, most existing deep learning approaches depend on extensive high-quality single-cell or patch-level annotations, which are labor-intensive and costly to generate. To address these limitations, we previously introduced HistoTME, a weakly supervised deep learning framework that predicts the activity of cell type-specific transcriptomic signatures directly from whole slide H&E images of non-small cell lung cancer. This enables rapid, high throughput analysis of the TME composition from whole slide H&E images (WSI) without the need for segmenting and classifying individual cells. In this work, we present HistoTME-v2, a pan-cancer extension of HistoTME, applied across 25 solid tumor types, substantially broadening the scope of prior efforts. HistoTME-v2 demonstrates high accuracy for predicting cell type-specific transcriptomic signature activity from H&E images, achieving a median Pearson correlation of 0.61 with ground truth measurements in internal cross- validation on The Cancer Genome Atlas (TCGA), encompassing 7,586 WSIs, 6,901 patients, and 24 cancer types, and a median Pearson correlation of 0.53 on external validation datasets spanning 5,657 WSIs, 1,775 patients and 9 cancer types. Furthermore, HistoTME- v2 resolves the spatial distribution of key immune and stromal cell types, exhibiting strong spatial concordance with single-cell measurements derived from multiplex imaging (CODEX, IHC) as well as Visium spatial transcriptomics, spanning 259 WSI, 154 patients, and 7 cancer types. Overall, across both bulk and spatial settings, HistoTME-v2 significantly outperforms baselines, positioning it as a robust, interpretable and cost-efficient tool for TME profiling and advancing the integration of spatial biology into routine pathology workflows.

pathology↗

bioRxiv2023

Increased stromal densities of B cells, CD103+ cells, and CD163+ M2-like macrophages associate with poor clinical outcomes in BCG treated non-muscle invasive bladder cancer

Non-muscle invasive bladder cancer (NMIBC) constitutes a significant clinical challenge, with over 50% of patients experiencing poor clinical outcomes in the form of early recurrence or progression following treatment with Bacillus Calmette-Guerin (BCG) immunotherapy. The pre-treatment tumor immune microenvironment (TIME) is an established determinant of response to BCG. This study explores the spatial profiles of CD79a+ B cells, CD163+ M2-like macrophages, proliferating and tissue-resident phenotypes of T cells, along with PD-1/PD-L1 checkpoint expression in pre-BCG treatment tumors of 173 patients (139 males, 34 females). Multiplex immunofluorescence staining of a tumor tissue microarray, revealed elevated infiltration of CD79a+ B cells, CD163+ M2-like macrophages, CD103+ cells, and CD8+ T cells at the tumor invasive margins. Increased epithelial PD-L1 immune-checkpoint expression in tumors was observed in female and male patients who exhibited significantly shorter recurrence-free survival (RFS). Importantly, high CD79a+ B cell density in BCG-treated females in both stromal and epithelial compartments exhibited significantly shorter RFS and progression-free survival compared to males. Stromal CD79a+ B cell density was positively correlated with M2-like macrophages, CD8+ T cells, CD103+ cells and PD-1 expressing cells. CD79a+ B cells, CD103+ cells, and M2-like macrophage density were associated with higher grade and enriched in basal subtype tumor. This study highlights the significance of an understudied role of B cells and their cellular neighborhoods in the pre-treatment TIME and BCG-therapy response. Overall, findings from this study underscore the importance of considering sex-related immunobiological differences in the stromal compartments of bladder tumors towards the development of optimal therapeutic targeting strategies.

cancer biology↗

bioRxiv2021

Sexual dimorphism in outcomes of non-muscle invasive bladder cancer: a role of CD163+ M2 macrophages, B cells and PD-L1 immune checkpoint.

Non-muscle invasive bladder cancer (NMIBC) is significantly more common in men than women. However, female patients with NMIBC often present with more aggressive disease and do not respond as well to immunotherapy treatments. We hypothesized that sexual dimorphism in the tumor immune microenvironment (TIME) may contribute to the inferior clinical outcomes observed in female patients. To test this hypothesis, we interrogated the expression patterns of genes associated with specific immune cell types and immune regulatory pathways using tumor whole transcriptome profiles from male (n=357) and female (n=103) patients with NMIBC. High-grade tumors from female patients exhibited significantly increased expression of CD40, CTLA4, PDCD1, LAG3 and ICOS immune checkpoint genes. Based on the significant differences in expression profiles of these genes and the cell types that most commonly express these in the TIME, we evaluated the density and spatial distribution of CD8+Ki67+ (activated cytotoxic T cells), FoxP3+ (regulatory T cells), CD103+ (tissue resident T cells), CD163+ (M2-like tumor associated macrophages), CD79a+ (B cells), PD-L1+ (Programmed-Death Ligand-1) and PD-1+ cells using multiplexed immunofluorescence in an independent cohort of 332 patient tumors on a tissue microarray (n=259 males and n=73 females). Tumors from female patients showed significantly higher infiltration of CD163+ macrophages and PD-L1+ cells compared to tumors from male patients. Notably, increased infiltration of CD163+ macrophages and CD79a+ B cells independently associated with decreased recurrence free survival. Not only do these results have the potential to inform the rational utilization of immunomodulatory therapies based on the TIME of both male and female patients with NMIBC, these novel findings highlight the necessity of considering sexual dimorphism in the design of future immunotherapy trials.

immunology↗