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Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [scRNA-seq]

ABSTRACT: Despite advances in screening and prevention, cervical cancer remains a leading cause of cancer-related deaths worldwide, underscoring the need for better treatments. Here, we present a multi-cohort longitudinal study of human cervical tumors and the tumor microenvironment during chemoradiation therapy (CRT). Integrating RNA sequencing, single-cell transcriptomics, and in vivo validation, we define the cellular and molecular programs shaping cell interactions and document how CRT alters them. We identify multiple therapeutic targets in CRT-resistant tumors, notably MDM2, a key mediator of radiation responses in tumor and immune cells. MDM2 inhibition enhanced radiotherapy effects in HPV-positive, TP53 wild-type cervical cancer cells, improved radiation response and reshaped the immune landscape in preclinical models. These findings highlight the potential of combining MDM2 inhibition with CRT to overcome resistance and improve patient outcomes. Our data provides novel insights into therapy-induced changes in tumor and immune compartments, guiding new strategies against treatment-resistant HPV-positive cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297041 | GEO | 2025/11/10

REPOSITORIES: GEO

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Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [bulk RNA-seq]

Project description:Despite advances in screening and prevention, cervical cancer remains a leading cause of cancer-related deaths worldwide, underscoring the need for better treatments. Here, we present a multi-cohort longitudinal study of human cervical tumors and the tumor microenvironment during chemoradiation therapy (CRT). Integrating RNA sequencing, single-cell transcriptomics, and in vivo validation, we define the cellular and molecular programs shaping cell interactions and document how CRT alters them. We identify multiple therapeutic targets in CRT-resistant tumors, notably MDM2, a key mediator of radiation responses in tumor and immune cells. MDM2 inhibition enhanced radiotherapy effects in HPV-positive, TP53 wild-type cervical cancer cells, improved radiation response and reshaped the immune landscape in preclinical models. These findings highlight the potential of combining MDM2 inhibition with CRT to overcome resistance and improve patient outcomes. Our data provides novel insights into therapy-induced changes in tumor and immune compartments, guiding new strategies against treatment-resistant HPV-positive cancers.

2025-11-10 | GSE297038 | GEO

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

2023-05-31 | GSE233517 | GEO

Epigenetic therapy with hydralazine and magnesium valproate added to chemoradiation in cervical carcinoma.

Project description:As a number of epigenetic alterations have been described in cervical cancer which may participate in the development and progression of this tumor, and the primary treatment for locally advanced disease is concurrent chemoradiation, we wanted to evaluate the efficacy and safety of hydralazine and valproate added to radiation and cisplatin. In addition, the transcriptome changes induced by the epigenetic drugs were also evaluated. Keywords: Cervical Cancer, epigenetic therapy, valproate, hydralazine, transcriptional response, epigenetic drugs

2007-07-31 | GSE8604 | GEO

Clinical and genomic characterization of chemoradiation resistant HPV-positive squamous cell carcinoma

Project description:This study performed genomic sequencing on a rare phenotype of HPV-positive oropharyngeal squamous cell carcinoma which was resistant to standard of care platinum based chemoradiation treatment. Tissue was collected from archival FFPE when available from pretreatment and post treamtent samples from four patients and these were batch corrected to be compared to known HPV-positive tumors without recurrent disease

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Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [scRNA-seq]

Project description:Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [scRNA-seq]

| PRJNA1262429 | ENA

Prognostic Significance of Immune Cell Infiltration in Muscle Invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and 0712

Project description:Chemoradiation therapy (CRT) is a treatment for muscle invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers for response to CRT on 70 pre-treatment tumor samples from NRG/RTOG 0524 and 0712, two prospective trials of MIBC. Disease-free survival (DFS) and overall survival (OS) was estimated by Kaplan-Meier method and stratified by genes correlated with immune cell proportions and activation. Cox proportional hazards models were used to assess group differences. Sample clustering based on gene expression profiles driven by immune cell proportions demonstrated cluster 2 with a high percentage of immune cell content with significantly longer DFS (Hazard Ratio (HR): 0.53 (95% CI: 0.26 – 1.10), p=0.071) and OS (HR: 0.48 (95% CI: 0.24 – 0.97), p=0.040) than cluster 1 with a low percentage of immune cell content. Higher expression of T cell infiltration genes (CD8A and ICOS ) showed longer DFS (HR: 0.40 (95% CI: 0.21 – 0.75), p=0.005) and OS (HR: 0.49 (95% CI: 0.25 – 0.94), p=0.033). Higher expression of interferon gamma signaling (IDO1) also showed longer DFS (HR: 0.44 (95% CI: 0.24 – 0.88), p=0.021) and OS (HR: 0.49 (95% CI: 0.24 – 0.99), p=0.048). These findings have treatment implications that should be validated in CRT MIBC trials particularly those that integrate immunotherapy.

2023-12-31 | GSE245748 | GEO

Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [bulk RNA-seq]

Project description:Chemoradiation Reprograms Tumor Cells and Immune Microenvironment In Cervical Cancer [bulk RNA-seq]

| PRJNA1262424 | ENA

Project description:Following exposure to chemoradiation, EAC cells increase their mitochondrial content and associated metabolic processes, which drives treatment resistance. Inhibition of this response using clinically applicable inhibitors of ESRRA in combination with (chemo)radiation shows promising anti-tumor activities and could be further developed for clinical use.

2022-10-17 | GSE184654 | GEO

Addition of losartan to FOLFIRINOX and chemoradiation reduces immunosuppression-associated genes, Tregs and FOXP3+ cancer cells in locally advanced pancreatic cancer

Project description:Purpose: Adding losartan (LOS) to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) resulted in 61% R0 surgical resection in our phase II trial in patients with locally advanced pancreatic cancer (LAPC). Here we identify potential mechanisms of benefit by assessing the effects of neoadjuvant losartan on the stromal tumor microenvironment. Experimental Design: We performed a gene expression and immunofluorescence (IF) analysis using archived surgical samples from patients treated with LOS+FFX+CRT (NCT01821729), FFX+CRT (NCT01591733) or surgery upfront, without any neoadjuvant therapy. We also conducted a longitudinal analysis of multiple biomarkers in the plasma of treated patients. Results: In comparison to FFX+CRT, LOS+FFX+CRT downregulated immunosuppression and pro-invasion genes. Overall survival (OS) was associated with DC and antigen presentation genes for patients treated with FFX+CRT, and with immunosuppression and invasion genes or DC– and blood vessel-related genes for those treated with LOS+FFX+CRT. Furthermore, losartan induced specific changes in circulating levels of IL-8, sTie2 and TGF-. IF revealed significantly less residual disease in lesions treated with LOS+FFX+CRT. Lastly, patients with a complete/near complete pathological response in the LOS+FFX+CRT-treated group had reduced CD4+FOXP3+ regulatory T cells (Tregs), fewer immunosuppressive FOXP3+ cancer cells (C-FOXP3) and increased CD8+ T cells in PDAC lesions. Conclusions: Adding losartan to FFX+CRT reduced pro-invasion and immunosuppression related genes which were associated with improved survival in patients with LAPC. Lesions from responders in the LOS+FFX+CRT-treated group had reduced Tregs, decreased C-FOXP3 and increased CD8+ T cells. These findings suggest that losartan may potentiate the benefit of FFX+CRT by reducing immunosuppression.

2023-02-02 | GSE222788 | GEO

Gene expression characterization of HPV positive head and neck cancer to predict response to Chemoradiation

Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.

2014-12-19 | E-GEOD-40020 | biostudies-arrayexpress

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