INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression

Cancer Research Communications, Journal Year: 2024, Volume and Issue: 4(2), P. 571 - 587

Published: Feb. 8, 2024

Abstract Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA 23 and 39 tumors (n = 62) was sequenced uncover transcriptomic profiles. Differential expression followed gene set enrichment analysis performed outline top enriched biological process in compared entity. INHBA, highest overexpressed tumor, knocked down. Functional assays (migration, proliferation, death, stemness) were conducted confirm target's oncogenic role. Correlation analyses reveal its impact on tumor microenvironment performed. We revealed epithelial-to-mesenchymal transition (EMT) is most OPSCC, INHBA (inhibin beta A subunit) being upregulated gene. knockdown downregulated of EMT transcription factors attenuated migration, stemness, death resistance cells. uncovered associates pro-tumor negatively correlating antitumor CD8+ T B cells while positively M1 macrophages. identified three miRNAs are putatively involved repressing expression. Our results indicate upregulation tumor-promoting. propose as an attractive target for treatment INHBA-enriched patients ameliorate prognosis. Significance: have poorer due pathways. reveals significant differences between identifying key OPSCC's crucial promoting EMT, immunosuppressive environment, suggesting potential

Language: Английский

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Identification of potential genes associated with metastasis in osteosarcoma: an integrated bioinformatics analysis

MUSCULOSKELETAL SURGERY, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

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Exploring the Role of Cellular Interactions in the Colorectal Cancer Microenvironment

Journal of Immunology Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Colorectal cancer (CRC) stands as one of the tumors with globally high incidence and mortality rates. In recent years, researchers have extensively explored role tumor immune microenvironment (TME) in CRC, highlighting crucial influence cell populations driving progression shaping therapeutic outcomes. The TME encompasses an array cellular noncellular constituents, spanning cells, myeloid tumor-associated fibroblasts, among others. However, composition within is highly dynamic, evolving throughout different stages progression. These shifts subpopulation proportions lead to a gradual transition response, shifting from early antitumor growth late-stage environment that supports survival. Therefore, it further investigate understand complex interactions various TME. this review, we explore key components varying origins, subpopulations shared elements CRC TME, examining their interconnections critical considerations for developing personalized precise immunotherapy strategies.

Language: Английский

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Immune mediated support of metastasis: Implication for bone invasion

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 967 - 991

Published: July 14, 2024

Abstract Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once patient diagnosed with bone metastasis, the patient's quality of life overall survival are significantly reduced owing to wide range morbidities increasing difficulty treatment. Many studies have shown that closely related microenvironment, especially immune microenvironment. However, effects cells microenvironment on remain unclear. Here, we described changes during discussed their mechanisms. Osteoblasts, adipocytes, other non‐immune were also included. This review summarized existing treatment methods potential therapeutic targets, provided insights for future cancer metastasis.

Language: Английский

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Multi‐omics profiling reveals key factors involved in Ewing sarcoma metastasis

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients metastasis at diagnosis. Mechanisms leading to remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors metastases from a spontaneous mouse model using multi‐omics approach. Combining transcriptomics, proteomics, methylomics analyses, identified signaling cascades candidate genes enriched in that could be modulating aggressiveness EWS. Phenotypical validation of two these candidates, cyclic AMP‐responsive element‐binding protein 1 (CREB1) lipoxygenase homology domain‐containing (LOXHD1), showed an association migration clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst metastatic‐enriched results. different omics datasets, FYVE, RhoGEF, PH 4 (FGD4) as target interconnecting biological layers (RNA, methylation status) whose high expression associated worse clinical outcome. Further studies will provide insight into mechanisms ultimately improve survival rates patients.

Language: Английский

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Clinical efficacy of the HIV protease-inhibitor Indinavir in combination with chemotherapy for advanced classic Kaposi’s sarcoma treatment: a single-arm, phase II trial in the elderly

Cancer Research Communications, Journal Year: 2024, Volume and Issue: 4(8), P. 2112 - 2122

Published: July 19, 2024

Abstract Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against have only temporary efficacy. We previously shown that indinavir, HIV protease-inhibitor direct antiangiogenic antitumor activity, safe effective patients early CKS, effects are less prominent advanced disease, probably due to larger tumor mass. Therefore, clinical response indinavir was assessed CKS after debulking chemotherapy. This monocentric phase 2 trial elderly progressive/advanced treated chemotherapy combined, followed by maintenance alone. Secondary endpoints included safety biomarker evaluation. All evaluable (22) responded therapy. Out of these, 16 entered phase. The overall rate at end 75% (estimated median response-duration 43 months). Moreover, most responders showed further improvements (lesion number/nodularity) during post-treatment follow-up. relapse, progressors did not require systemic therapy (including stabilization) remaining on study. Responders also immune status amelioration consistent B-cell increase positive changes other biomarkers, including anti-HHV-8 natural killer activity. In strategy combining high durable rates it could be rapidly adopted for management these patients. Significance: phase-2 protease inhibitor may boost extend duration progressive sarcoma, without additional toxicity. Further, seen suggests better control HHV-8 infection tumor-cell killing. Thus, combined represent important tool

Language: Английский

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Single‐cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(19)

Published: Oct. 1, 2024

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment cellular communications of lymph metastasized tumours determine tumour progression therapeutic effect, but ecosystems about (LNM) for NPC patients remain poorly characterized. Here, we integrated transcriptomes 47,618 single cells from eight samples related LNM. dynamic immune immunosuppressive including T cells, myeloid B were observed metastatic compared with primary tumours. Additionally, heterogeneity epithelial was also revealed, several clusters expression programs that associated progression-free survival identified. our data revealed complex intercellular metastasis. rewiring CCL signalling which plays an important role further Altogether, systematically characterized ecosystem tumours, may shed light on development a strategy improve clinical outcomes

Language: Английский

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An Artificial Intelligence Model for Profiling the Landscape of Antigen-binding Affinities of Massive BCR Sequencing Data

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

The interaction between antigens and antibodies (B cell receptors, BCRs) is the key step underlying function of humoral immune system in various biological contexts. capability to profile landscape antigen-binding affinity a vast number BCRs will provide powerful tool reveal novel insights at unprecedented levels yield tools for translational development. However, current experimental approaches profiling antibody-antigen interactions are costly time-consuming, can only achieve low-to-mid throughput. On other hand, bioinformatics field antibody informatics mostly focus on optimization given known binding antigens, which very different research question limited scope. In this work, we developed an innovative Artificial Intelligence tool, Cmai, address prediction that be scaled high-throughput sequencing data. Cmai achieved AUROC 0.91 our validation cohort. We devised biomarker metric based output from applied BCR found that, during immune-related adverse events (irAEs) caused by immune-checkpoint inhibitor (ICI) treatment, immunity preferentially responsive intracellular organs affected irAEs. contrast, extracellular malignant tumor cells inducing B infiltrations, infiltrating have greater tendency co-localize with expressing these antigens. further abundance antigen-targeting predictive ICI treatment response. Overall, approach filled gap not addressed works nor such as AlphaFold3 predict structures complexes proteins bind.

Language: Английский

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Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/Neu B Cell Peptide-Based Vaccine Her-Vaxx and to Prevent Immune Evasion

Published: Nov. 22, 2023

The targeting-Her-2/neu therapy by passive application with trastuzumab is associated acquired resistance and subsequent metastasis development, attributed to upregulation of tumoral PD-L1 expression downregulation Her-2/neu. We aimed investigate this association, following active immunization our recently constructed B cell–peptide based Her-2/neu vaccines in both preclinical clinical settings. Immunohistochemistry (IHC), fluorescence situ hybridization (FISH), combined positive score (CPS), were applied evaluate using a murine syngeneic tumor model for lung metastases, biopsies from gastric cancer patient disease progression. A significant concomitant reduction was observed the vaccinated mice, after 7 but not 4 weeks metastases development. increase tumor-infiltrating lymphocytes at time points. Downregulation patient’s primary progression point prior vaccination (Her-2/neu IHC: 3 0, FISH: 4.98 1.63; CPS: 0% 5%). Our results further underline need combination targeting prevent formation immune evasion negative cells.

Language: Английский

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Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 287 - 287

Published: Dec. 24, 2023

Her-2/neu-targeting therapy by passive application with trastuzumab is associated acquired resistance and subsequent metastasis development, which attributed to the upregulation of tumoral PD-L1 expression downregulation Her-2/neu. We aimed investigate this association, following active immunization our recently constructed B-cell peptide-based Her-2/neu vaccines in both preclinical clinical settings. Immunohistochemistry (IHC), fluorescence situ hybridization (FISH), combined positive score (CPS) were applied evaluate using a murine syngeneic tumor model for lung metastases biopsies from gastric cancer patient disease progression. A significant concomitant reduction was observed vaccinated mice after 45 days, but not 30 development. increase tumor-infiltrating B lymphocytes at time points. The patient’s primary progression point prior vaccination (Her-2/neu IHC: 3 0, FISH: 4.98 1.63; CPS: 0% 5%). Our results further underline need combination targeting prevent formation immune evasion Her-2/neu-positive PD-L1-negative cells.

Language: Английский

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