The lactate receptor HCAR1 drives the recruitment of immunosuppressive PMN-MDSCs in colorectal cancer

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Language: Английский

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LCAT in Cancer Biology: Embracing Epigenetic Regulation, Immune Interactions, and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1453 - 1453

Published: Feb. 10, 2025

Lecithin cholesterol acyltransferase (LCAT) is a crucial enzyme in high-density lipoprotein (HDL) metabolism that often dysregulated cancers, affecting tumor growth and therapy response. We extensively studied LCAT expression various malignancies, linking it to clinical outcomes genetic/epigenetic alterations. analyzed multiple cancers used the Cox regression model correlate with patient survival metrics, including overall (OS), disease-specific (DSS), progression-free interval (PFI). also examined copy number variations (CNVs), single-nucleotide (SNVs), DNA methylation, N6-methyladenosine (m6A) modifications of their connections immune responses drug sensitivity. varies among correlates outcomes. Low linked poor prognosis low-grade glioma (LGG) liver hepatocellular carcinoma (LIHC), while high associated better adrenocortical (ACC) colon adenocarcinoma (COAD). In kidney renal papillary cell (KIRP) uterine corpus endometrial (UCEC), CNV methylation levels are prognostic markers. interacts m6A modifiers molecules, suggesting role evasion as biomarker for immunotherapy chemotherapeutic IC50 values, indicating potential predicting treatment ACC COAD, may promote growth, LGG LIHC, inhibit progression. activity regulation could be new cancer target. As key molecule lipid metabolism, modulation, progression, significant. Our findings provide insights into biology support development personalized strategies.

Language: Английский

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High baseline levels of PD-L1 reduce the heterogeneity of immune checkpoint signature and sensitize anti-PD1 therapy in lung and colorectal cancers

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

Immune checkpoint blockade (ICB) therapy only induces durable responses in a subset of cancer patients. The underlying mechanisms such selective efficacy remain largely unknown. By analyzing the expression profiles immune molecules different statuses murine tumors, we found that tumor progression generally randomly upregulated multiple checkpoints, thus increased Heterogeneity Signature (HIS) and resulted immunotherapeutic resistance. Interestingly, overexpressing one pivotal hindered upregulation majority other genes during via suppressing interferon γ, resulting HIS-low. Indeed, PD-L1 high-expression sensitized baseline large tumors to anti-PD1 without altering sensitivity small tumors. In line with these preclinical results, retrospective analysis phase III study involving patients non-small cell lung (NSCLC) revealed proportion score (TPS) ≥ 50% more reliably predicted therapeutic response NSCLC volume (BTV)-large compared BTV-small. Notably, TPS combined BTV significantly improved predictive accuracy. Collectively, data suggest HIS reflects dynamic features evasion dictates ICB size-dependent manner, providing potential novel strategy improve precision ICB. These findings highlight application earlier stages integration may immediately patient stratification prediction performance clinic.

Language: Английский

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Programmed Cell Death Ligand as a Biomarker for Response to Immunotherapy: Contribution of Mass Spectrometry-Based Analysis

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 1001 - 1001

Published: March 17, 2025

Immune checkpoint inhibition is a major component in today’s cancer immunotherapy. In recent years, the FDA has approved number of immune inhibitors (ICIs) for treatment melanoma, non-small-cell lung, breast and gastrointestinal cancers. These inhibitors, which target cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), ligand (PD-L1) checkpoints have assumed leading role The same exert significant antitumor effects by overcoming tumor evasion reversing T-cell exhaustion. initial impact this therapy was justly described as revolutionary, however, clinical well research data followed demonstrated that these innovative drugs are costly, associated with potentially severe adverse effects, only benefit small subset patients. limitations encouraged enhanced efforts to identify predictive biomarkers stratify patients who most likely from form therapy. discovery characterization class pivotal guiding individualized against various forms cancer. Currently, there three FDA-approved biomarkers, none on its own can deliver reliable precise response Present literature identifies absence poor understanding mechanisms behind resistance main obstacles facing ICIs present text, we discuss dual PD-L1 biomarker immunotherapy an checkpoint. contribution mass spectrometry-based analysis, particularly protein post-translational modifications performance underlined.

Language: Английский

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Dynamics of tertiary lymphoid structures and immune cross talk in early versus advanced colorectal cancer: potential implications for immunotherapy

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(6)

Published: April 26, 2025

Abstract Background Irrespective of microsatellite status, immune checkpoint inhibitor therapy shows superior efficacy in early-stage colorectal cancer (CRC) compared to advanced cases. The distinctions the tumor microenvironment (TME) and tertiary lymphoid structure (TLS) between early- advanced-stage CRC may represent a critical factor, yet remain incompletely elucidated. Methods We comprehensively analyzed single-cell RNA sequencing data, bulk transcription data pathological tissue investigate dynamic changes TME. features TLS tumors their potential impact on immunotherapy were explored using three in-house cohorts. Results provided fine maps landscape early CRC. Significant functional differences identified CD4 + Tfh BGC cells revealed CXCL13 expression CD8 Tex cells, along with CD40–CD40L interactions could be key regulators functionality subsequently affect response immunotherapy. Conclusions Our research shed light multilayered dysfunction elucidates alterations during progression CRC, providing insights for studies exploration target

Language: Английский

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Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors

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

Published: Nov. 26, 2024

Immunotherapy has become a global focus in cancer treatment and research, with promising results from targeting immune checkpoints tumors like non-small cell lung cancer, colon melanoma. However, resistance to checkpoint inhibitors (ICIs) remains significant challenge. Traditional Chinese medicine (TCM), known for its low toxicity minimal side effects, shows promise enhancing when combined modern therapies. This study reviews recent research on ICIs mechanisms highlights TCM's potential overcoming this resistance, aiming improve efficacy while minimizing toxicity.

Language: Английский

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Colorectal cancer patients-derived immunity-organoid platform unveils cancer-specific tissue markers associated with immunotherapy resistance

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(12)

Published: Dec. 4, 2024

Abstract Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged promising treatments; however, their efficacy largely restricted to subgroup microsatellite instable (MSI) CRCs. In contrast, stable (MSS) CRCs, which account for majority cases, exhibit variable and generally weaker response ICIs, with only subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive immunotherapy crucial refining patient selection overcoming treatment resistance. this study, we developed clinically relevant CRC organoids autologous immune system interaction platforms model ICI response. We conducted comprehensive molecular characterization both responder non-responder models, identifying CST that predict Validation these findings was performed using an independent cohort specimens through multiplex immunofluorescence. Furthermore, demonstrated knocking out key gene from identified signature in resistant restored sensitivity induced T-cell-mediated apoptosis. Overall, our results provide insights into mechanisms underlying resistance suggest new enhancing selection. These may pave way therapeutic options MSS patients, potentially broadening individuals eligible immunotherapy.

Language: Английский

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Dysregulation of systemic immunity in colorectal cancer and its clinical applications as biomarkers and therapeutics

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 204, P. 104543 - 104543

Published: Oct. 24, 2024

Language: Английский

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