Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(4), P. 369 - 381

Published: Feb. 9, 2024

Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) senescent-like neutrophils T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or ablation. De novo post-translational acetylation AR, HOXB13, H2A at K609, K13, K130, respectively, phosphorylation H4 Y88 have emerged as key epigenetic modifications associated castration-resistant PC (CRPC). The resulting chromatin changes integrated into cellular processes via ACK1, ATPF1A, SREBP1 Y267, Y284, Y243/Y246, Y673/Y951, respectively. In this review, we discuss how these de alterations drive resistance efforts aimed targeting regulators may overcome immune suppression PC.

Language: Английский

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One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor

Science Advances, Journal Year: 2025, Volume and Issue: 11(5)

Published: Jan. 29, 2025

Cancer immunotherapies rely on CD8 + cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency human murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer one-dimensional bamboo-like multisegmented manganese dioxide@manganese–bismuth vanadate (BMMBV) to boost multiple branches immune responses targeting MHC-I–deficient tumors. BMMBV markedly augments sonodynamic activity contributed by heteroatoms the lattice bismuth with narrowing bandgaps. Under sonoirradiation, enhances antigen spreading emission adjuvant signals, which potentiate dendritic cell maturation, thereby eliciting high aptitude CTLs. This therapy substantially up-regulates MHC expression cells, are reversely sensitive Alongside, extensive innate complement CTLs eliminating mouse study offers a reinforced strategy against antigen-loss immune-evasive tumor.

Language: Английский

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SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 4, 2024

Abstract Mutations that decrease or increase the activity of tyrosine phosphatase, SHP2 (encoded by PTPN11 ), promotes developmental disorders and several malignancies varying phosphatase activity. We uncovered is a distinct class an epigenetic enzyme; upon phosphorylation kinase ACK1/TNK2, pSHP2 was escorted androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation histones H3 at Tyr54) marks trigger transcriptional program AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, knock-in mice, ACK1 knockout mice presented dramatic in pY54-H3, leading loss AR transcriptome. In contrast, prostate tumors high pACK1 exhibited progressive downregulation levels higher expression correlated disease severity. Overall, pSHP2/pY54-H3 signaling acts as sentinel homeostasis, explaining not only growth retardation, genital abnormalities infertility among NSML but also significant upregulation cancer patients.

Language: Английский

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Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients

Cells, Journal Year: 2024, Volume and Issue: 13(9), P. 782 - 782

Published: May 3, 2024

CXCR4, JUNB and PD-L1 are implicated in cancer progression metastasis. The current study investigated these biomarkers CTCs isolated from metastatic prostate (mPCa) patients at the RNA protein levels. were 48 mPCa using Ficoll density gradient ISET system (17 out of 48). (CK/PD-L1/CD45) (CK/CXCR4/JUNB) phenotypes identified two triple immunofluorescence stainings followed by VyCAP platform analysis. Molecular analysis was conducted with an EpCAM-dependent method for 25/48 patients. CK-8, CK-18, CK-19, JUNB, PD-L1, B2M (reference gene) analyzed RT-qPCR. (CK+/PD-L1+/CD45-) (CK+/CXCR4+/JUNB+) most frequent (61.1% 62.5%, respectively). Furthermore, (CK+/CXCR4+/JUNB-) phenotype correlated poorer progression-free survival [(PFS), HR: 2.5, p = 0.049], while linked to decreased overall [(OS), 262.7, 0.007]. revealed that 76.0% samples positive CK-8,18, 19, 28.0% 44.0% 48.0% PD-L1. Conclusively, highly expressed CXCR4 expression associated PFS, OS, providing new potential clinical relevance.

Language: Английский

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Immunotherapy targeting PD‑1/PD‑L1: A potential approach for the treatment of cancer bone metastases (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 64(4)

Published: Feb. 13, 2024

Immune checkpoint molecules, such as programmed cell death 1 (PD‑1) and ligand (PD‑L1), have a critical role in regulating immune responses, including tumor tissues. Monoclonal antibodies against these known inhibitors (ICIs), been shown to be effective variety of cancers; however, significant patient populations are resistant treatment. Clinical studies date that ICIs less cancer patients with bone metastases. The effect anti‑PD‑1/PD‑L1 on metastases, assessed by the metastasis‑specific response classification criteria, was relatively low. In addition, presence metastases showed trend toward worse progression‑free survival overall treated ICIs. To improve efficacy several combination therapies under investigation certain reported better responses. present review summarizes current understanding effects based clinical preclinical studies.

Language: Английский

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MLXIPL associated with tumor-infiltrating CD8+ T cells is involved in poor prostate cancer prognosis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Introduction Within tumor microenvironment, the presence of preexisting antitumor CD8+ T Q7 cells have been shown to be associated with a favorable prognosis in most solid cancers. However, case prostate cancer (PCa), they linked negative impact on prognosis. Methods To gain deeper understanding contribution infiltrating poor PCa, infiltration levelsof were estimated using TCGA PRAD (The Cancer Genome Atlas Prostate Adenocarcinoma dataset) and MSKCC (Memorial Sloan Kettering Center) cohorts. Results Bioinformatic analyses revealed that likely influence PCa through increased expression immune checkpoint molecules enhanced recruitment regulatory cells. The MLXIPL was identified as gene expressed response cell found prognostic role examined two cohorts: (p = 2.3E-02) cohort 1.6E-02). Subsequently, confirmed an unfavorable evidenced by independent study (hazard ratio [HR] 2.57, 95% CI: 1.42- 4.65, p 1.76E-03). Discussion In summary, findings suggested related tumor-infiltrating facilitated PCa.

Language: Английский

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Identification of pyrimidine metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical treatment in prostate cancer

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: Jan. 13, 2025

Background We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, found significant differences pyrimidine metabolites. The PMGs is associated with clinical prognosis several cancers, but its biological role PCa still unclear.

Language: Английский

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Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment

Small Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

A variety of factors, such as dietary habits, the external environment, and individual genetic differences, can lead to development cancer. While chemotherapy radiotherapy are commonly used for cancer treatment, drug resistance side effects prevalent issues. Therefore, there is an urgent need find new treatment modalities. Studies have shown that a significant increase in apoptotic cells (ACs) within tumor microenvironment (TME). The process phagocytosis helps maintain homeostasis by engulfing removing these ACs from organism promptly, which referred efferocytosis. However, it has been observed excessive efferocytosis promote formation immunosuppressive TME, detrimental therapy. Thus, inhibiting enhance immune shows promise direction tumors. As researchers gradually uncover molecular mechanisms efferocytosis, various small‐molecule inhibitors monoclonal antibodies actively being assessed clinical trials. Targeting anticipated emerge promising approach treatment. In this review, intricate steps involved explored current drugs targeting outlined.

Language: Английский

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Ultrasound-guided percutaneous radiofrequency ablation combined with anti-PD-1 for the treatment of prostate cancer: an experimental study

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 24, 2025

Background This study seeks to investigate the potential synergistic effects of combining ultrasound-guided percutaneous radiofrequency ablation with anti-PD-1 therapy on prostate cancer, utilizing animal models. Methods A mouse model cancer was established by subcutaneous injection 1 × 10 6 Myc-Cap cells right side FVB mice. When volume tumors reached about 400mm 3 , mice were randomly divided into four groups and received corresponding intervention treatments. Among them, Group blank control group, 2 simple treatment 4 is group that combined under ultrasound guidance. The growth observed in after each tumor tissues collected, immune status analyzed through flow cytometry, immunohistochemistry, immunofluorescence, other methods. Results Compared groups, significantly reduced weight tumors, demonstrating more effective suppression. At same time, combination can promote aggregation T-cells within increase proportion cytotoxic T-cells, M1 macrophages iNOS expression, decrease M2 Arg expression local area tumors. Conclusion Local improve therapeutic effect PD-1 monoclonal antibody. Our preliminary results suggest ablation, treatment, produces effects. These may be driven changes cell populations tumor’s immunosuppressive microenvironment.

Language: Английский

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Recent developments on checkpoint inhibitors, CAR T cells, and beyond for T cell-based immunotherapeutic strategies against cancer

Journal of Oncology Pharmacy Practice, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Objective There was a dire need to construct review of the recent developments on Immune checkpoint inhibitors (ICIs), CAR T Cells, and other approaches for cell-based immunotherapeutic strategies against cancer as has become one most fatal diseases that is responsible causing several deaths per annum. Data sources Multiple published data acquired from high-impact factor journal articles. summary clinical have been in use today such radiotherapy, chemotherapy immunotherapy treat different types. Among novel management strategies, role by cells immensely important. Cancer revolutionized treatment it basically utilizes body's immune system cancer. At forefront this revolution, are considered fundamental components system. Conclusions The current explores therapeutic potential fight applying various ICIs (PD-1/PD-L1, CTLA-4, TIGIT, BTLA, TIM3, LAG3) adoptive cell therapy. stimulate existing anti-tumor T-cell response way removing inhibitors. On hand, therapy (ACT) patient's modified identify attack tumor cells. Furthermore, also highlights significant successes observed with these therapies, notably PD-1 blockade tumors. Moreover, vaccination, bispecific antibodies cytokine enhance antitumor activity. Therapeutic vaccines expose tumor-associated antigens training then cells, showing promising results types cancers prostate melanoma. While, accompanied cytokines interleukin-2 (IL-2) activity proliferation, thereby boosting overall response. Lastly, future immunotherapy, envisioning advancements design gene editing techniques can efficacy across broader spectrum cancers.

Language: Английский

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