Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 28, 2024

Tertiary lymphoid structures (TLSs) are defined as aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary (SLOs), the formation of TLSs relies on interaction between tissue inducer (LTi) cells and organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature TLSs, which may lead differences their functions. Growing evidence suggests that associated with various diseases, such cancers, autoimmune transplant rejection, chronic inflammation, infection, even ageing. However, detailed mechanisms behind these clinical associations not yet fully understood. The by TLS maturation localization affect immune function also unclear. Therefore, it necessary enhance understanding development at cellular molecular level, allow us utilize them improve microenvironment. In this review, we delve into composition, mechanism, potential therapeutic applications TLSs. Furthermore, discuss implications role markers response prognosis. Finally, summarize methods for detecting targeting Overall, provide comprehensive aim develop more effective strategies.

Language: Английский

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T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105154 - 105154

Published: May 14, 2024

Language: Английский

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The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 396 - 396

Published: Jan. 17, 2024

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, current ways recognizing them. A comprehensive literature was performed using PubMed/Medline, Scopus, EMBASE databases. significant area interest cancer research involves targeting immune checkpoint molecules, particularly triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations accurately predicting response. In this context, (TLSs) emerge as a biomarker also promising predictive marker for TLSs are ectopic formations or neo-organogenesis that can develop after prolonged exposure inflammatory signals mediated by chemokines cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone (PR) expression, but positively associated higher pathologic complete response rate improved overall survival. certain scenarios, TLS-positive tumors were outcomes regardless PDL-1 (programmed cell death ligand 1) expression TILs (tumor-infiltrating lymphocytes).

Language: Английский

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Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma

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

Published: Oct. 22, 2024

Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T receptor sequencing, we profile tissues from ESCC patients accepting and characterize microenvironment context. CXCL13+CD8+ Tex cells, a subset exhausted CD8+ revealed highly infiltrate in pre-treatment tumors show prominent progenitor exhaustion phenotype post-treatment samples responders. We validate cells as predictor improved reveal CXCL13 potentiate anti-PD-1 efficacy vivo. Post-treatment non-responders enriched for notably remarkable TNFRSF4+CD4+ Tregs activated immunosuppressive function significant clone expansion. Several critical markers therapeutic resistance also identified, including LRRC15+ fibroblasts SPP1+ macrophages, which may recruit form an landscape. Overall, our findings unravel immune features distinct treatment, providing rationale optimizing individualized neoadjuvant strategy ESCC. The tumour (ESCC) remain be explored. single TCR on pre- post- identifies presence enrichment marker resistance.

Language: Английский

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Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer

Journal of Cannabis Research, Journal Year: 2024, Volume and Issue: 6(1)

Published: May 16, 2024

Abstract Cancer comes in second place on the list of causes death worldwide. In 2018, 5-year prevalence breast cancer (BC), prostate (PC), and colorectal (CRC) were 30%, 12.3%, 10.9%, respectively. Cannabinoids are chemicals derived from Cannabis sativa plant; most investigated cannabinoids cannabinol, delta 9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol. humans, endogenous endocannabinoid system consists endocannabinoids, receptors (CBs), enzymes that degrade endocannabinoids. this review, we will review recent literature for evidence discusses role cannabis treatment three types neoplasms mentioned. Studies have proved BC cells express CB receptors; many in- vivo studies showed cause apoptosis inhibit proliferation migration. Also, researchers found treating mice with THC JWH-133 (CB2 receptor agonist) slowed tumor growth. Regarding CRC, cannabidiol was to decrease viability chemotherapy-resistant CRC metastasis by antagonizing G-protein-coupled 55 (GPR55; a novel cannabinoid receptor) necessary metastasis. Moreover, had anti-angiogenetic effects reducing expression vascular endothelial growth factor (VEGF) addition anti-inflammatory effects. Finally, demonstrated PC highly CB1 CB2 capable inhibiting release exosomes microvesicles related progression. also antiproliferative, anti-invasive, anti-fibroblastic, cell cycle arrest, proapoptotic cells.

Language: Английский

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Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 1, 2025

ABSTRACT Background Immune checkpoint inhibitors (ICIs) have achieved great success; however, a subset of patients exhibits no response. Consequently, there is critical need for reliable predictive biomarkers. Our focus on CDC42, which stimulates multiple signaling pathways promoting tumor growth. We hypothesize that an impaired function CDC42 may serve as indicator patient's response to ICI therapy. Methods consider and its downstream binding effector proteins gene set, mutations in these components could lead defective function. To elucidate the biomarker within we curated comprehensive discovery dataset included seven treatment cohorts. And two cohorts validation. explored mechanism based The Cancer Genome Atlas database. also examined whether combining inhibitor with enhance ICI's efficacy. Results Mutations set were associated improved overall survival progression‐free survival. Furthermore, our analysis immune landscapes among different statuses supports role biomarker. Animal experiments revealed combination (ML141) anti‐PD‐1 blockade can additively reduce Conclusions study suggests potentially novel clinical treatment. This finding provides insights into potential use more efficient patient

Language: Английский

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Comprehensive biomarker profiles in hematological malignancies: improving diagnosis, prognosis, and treatment

Biomarkers in Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 27, 2025

Hematological malignancies present substantial challenges in clinical practice due to their heterogeneity and complex biological profiles. In these diseases, biomarkers – measurable indicators of states are indispensable for diagnosis, prognosis, therapeutic decision-making. Emerging significantly improving outcomes hematological cancers by enhancing early detection, refining prognostic assessments, enabling personalized treatment approaches, optimizing overall patient management. This progress translates into better more effective strategies treat manage malignancies. The field biomarker discovery has developed from basic morphological cytogenetic markers advanced molecular techniques, including polymerase chain reaction (PCR) next-generation sequencing (NGS), which have enhanced diagnostic accuracy led the development targeted therapies. Additionally, recent advent technologies like mass spectrometry single-cell RNA enables comprehensive profiling reveals novel that were previously undetectable. Our aim this manuscript is provide a overview immunohematological biomarkers, applications, future directions field.

Language: Английский

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The evolving role of B cells in malignancies

Human Immunology, Journal Year: 2025, Volume and Issue: 86(3), P. 111301 - 111301

Published: March 25, 2025

Language: Английский

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The role of immunotherapy in targeting tumor microenvironment in genitourinary cancers

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

Genitourinary (GU) cancers, including renal cell carcinoma, prostate cancer, bladder and testicular represent a significant health burden are among the leading causes of cancer-related mortality worldwide. Despite advancements in traditional treatment modalities such as chemotherapy, radiotherapy, surgery, complex interplay within tumor microenvironment (TME) poses substantial hurdles to achieving durable remission cure. The TME, characterized by its dynamic multifaceted nature, comprises various types, signaling molecules, extracellular matrix, all which instrumental cancer progression, metastasis, therapy resistance. Recent breakthroughs immunotherapy (IO) have opened new era management GU offering renewed hope leveraging body's immune system combat more selectively effectively. This approach, distinct from conventional therapies, aims disrupt cancer's ability evade detection through mechanisms checkpoint inhibition, therapeutic vaccines, adoptive transfer therapies. These strategies highlight shift towards personalized medicine, emphasizing importance understanding intricate dynamics TME for development targeted treatments. article provides an in-depth overview current landscape with focus on IO targeting specific types TME. By exploring roles their impact this review underscore transformative potential targeting, effective options patients thereby improving outcomes quality life.

Language: Английский

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CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance

International Journal of Inflammation, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: Sept. 17, 2022

Chemokines and their receptors play important roles in the pathophysiology of many diseases by regulating cellular migration major inflammatory immune players. The CXC motif chemokine subfamily is second largest family, it further subdivided into ELR (ELR+) non-ELR (ELR-) chemokines, which are effective chemoattractants for neutrophils lymphocytes/monocytes, respectively. These chemokines expected to have a significant impact on wide range lung diseases, or immunological underpinnings. As result, manipulations this using small molecular agents other means been explored potential therapeutic benefit setting several pathologies. Furthermore, encouraging preclinical data has necessitated progression few these drugs clinical trials order make most use interventions development viable targeted therapeutics. current review presents understanding ligands (CXCLs) cognate (CXCRs) pathogenesis such as allergic rhinitis, COPD, fibrosis, cancer, pneumonia, tuberculosis. benefits pharmacological CXCL/CXCR axis also discussed.

Language: Английский

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