PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 29, 2024

Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 checkpoint blockade (ICB) with chemotherapy shown promising efficacy in both early metastatic triple-negative cancer, although only a subset of patients experiences durable responses. Identifying responders optimizing drug selection are therefore critical. The effectiveness immunotherapy depends on tumor-intrinsic factors the extrinsic cell-cell interactions within tumor microenvironment (TME). This review systematically summarizes key findings from clinical trials ICBs cancer examines mechanisms underlying expression regulation. We also highlight recent advances identifying potential biomarkers for therapy emerging evidence TME alterations following treatment. Among these, quantity, immunophenotype, spatial distribution tumor-infiltrating lymphocytes stand out as biomarkers. Additionally, we explore strategies to enhance aiming support development personalized approaches tailored unique characteristics each patient's tumor.

Language: Английский

---

A Case‐Driven Multi‐Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia

European Journal Of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated and clinical dynamics of CLL during 16 months monotherapy by analyzing blood samples from two patients who continued having cells in peripheral treatment. At diagnosis, burden within B cell compartment was found 55% (pt1) 86% (pt2) for dominant clones. following these clones still constituted 66% 89%, respectively. Utilizing multi-omic methodologies at DNA RNA levels, including single-cell transcriptomics, we aimed establish a comprehensive framework multi-omics analysis longitudinal response evaluation. The presented study revealed genomically stable disease treatment, but intensified expression genes involved pathways related apoptosis, cellular stress canonical NF-κB signaling diagnosis

Language: Английский

---

Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions

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

Published: Feb. 26, 2025

Triple-negative breast cancer (TNBC) is a highly malignant tumor in women, characterized by high morbidity, mortality, and recurrence rates. Although surgical treatment, radiotherapy, chemotherapy are the mainstays of current treatment methods, heterogeneity TNBC results unsatisfactory outcomes with low 5-year survival Rapid advancements omics technology have propelled understanding molecular biology. The emergence single-cell RNA sequencing (scRNA-seq) spatial transcriptomics (ST) has significantly enhanced knowledge distribution, functionality, intercellular interactions various cell types within microenvironment, including cells, T B macrophages, fibroblasts. present study provides an overview technical characteristics scRNA-seq ST, highlighting their applications exploring heterogeneity, distribution patterns, interactions. This review aims to enhance comprehension at cellular level for development effective therapeutic targets.

Language: Английский

---

Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2795 - 2795

Published: March 20, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the absence estrogen receptors (ER), progesterone (PR), and HER2 expression. While TNBC relatively less common, accounting for only 10–15% initial diagnosis, due to its nature, it carries a worse prognosis in comparison hormone receptor-positive counterparts. Despite significant advancements screening, treatment cancer, remains important public health burden. Following with chemotherapy, surgery, radiation, over 40% patients experience relapse within 3 years achieve least benefit from post-mastectomy radiation. The tumor microenvironment environment (TME) pivotal initiation, progression, immune evasion, resistance, prognosis. TME complex network that consists cells, non-immune soluble factors located region adjacent modulates therapeutic response differentially between TNBC. mechanisms underlying radiation resistance remain unclear, immunosuppressive has been implicated chemotherapeutic resistance. Radiation therapy (RT) known alter TME; however, changes elicited are poorly date, whether these contribute unknown. This review delves into distinct characteristics TME, explores how RT influences dynamics, examines radiosensitization, radioresistance, responses.

Language: Английский

---

Development of oxidative stress- and ferroptosis-related prognostic signature in gastric cancer and identification of CDH19 as a novel biomarker

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Nov. 5, 2024

Ferroptosis is a unique mode of cell death that iron-dependent and associated with oxidative stress lipid peroxidation. Oxidative ferroptosis are essential mechanisms leading to metabolic abnormalities in cells have been popular areas cancer research. Initially, 76 ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from ferroptosis. Afterwards, optimal OFRGs screened using PPI networks, individuals separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed verified prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), CCN1. To further uncover potential biomarkers gastric (GC), examined expression level CDH19, investigated effects knocking down CDH19 on biological behavior GC cells, explored whether involved processes. According findings, low-risk scoring group less infiltration immune suppressive fewer occurrences escape dysfunction, greater efficacy chemotherapy immunotherapy, better survival outcomes. The qRT-PCR assay indicated was significantly higher cells. Through experiments, demonstrated can affect transcription levels ACSL4 GPX4, increase intracellular iron ion concentration accumulation reactive oxygen species (ROS), inhibit proliferation migration We developed an OFRG-related predict prognosis treatment responsiveness identified as possible therapeutic target for GC.

Language: Английский

---

Hyper-N-glycosylated SEL1L3 as auto-antigenic B-cell receptor target of primary vitreoretinal lymphomas

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 26, 2024

Abstract Primary vitreoretinal lymphoma (PVRL) is a rare subtype of DLBCL and can progress into primary central nervous system (PCNSL). To investigate the role chronic antigenic stimulation in PVRL, we cloned expressed B-cell receptors (BCR) from PVRL patients tested for binding against human auto-antigens. SEL1L3, protein with multiple glycosylation sites, was identified as BCR target 3/20 cases. SEL1L3 induces proliferation pathway activation aggressive cell lines. Moreover, conjugated to toxin killed exclusively cells respective BCR-reactivity. Western Blot analysis indicates occurrence hyper-N-glycosylation at aa 527 SEL1L3-reactive BCRs. The patient serum antibodies vitreous body biopsy diagnosis systemic manifestation relapse. VH4-04*07 used both manifestations highly conserved CDR3 regions. Both BCRs showed suggesting continued dependence on antigen stimulation. These results indicate an important by post-translationally modified auto-antigens genesis PVRL. They also provide basis new treatment approach targeting unique ultimate specificity.

Language: Английский

---