Journal of Cardiothoracic Surgery, Год журнала: 2024, Номер 19(1)
Опубликована: Ноя. 8, 2024
Observational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, treatment. However, few examined the causal association between them.
Язык: Английский
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Апрель 16, 2024
Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumor-associated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value various cancers. In recent years, concept maturity regarding been proposed mature TLS, characterized by well-developed germinal centers, exhibits more potent tumor-suppressive capacity with stronger significance. Meanwhile, evidence showed that can be induced therapeutic interventions during cancer treatments. Thus, evaluation induce its formation are critical issues current research. this review, we aim to provide comprehensive summary existing classifications for strategies capable inducing tumors.
Язык: Английский
Процитировано
24
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Авг. 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.
Язык: Английский
Процитировано
19
Journal of Clinical Investigation, Год журнала: 2025, Номер 135(7)
Опубликована: Март 31, 2025
Tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) are emerging solid-tumor indicators of prognosis and response to immunotherapy. Considering that tumorigenesis requires metabolic reprogramming subsequent TME remodeling, discovery TLS regulators is expected produce immunotherapeutic targets. To identify such regulators, we constructed a metabolism-focused sgRNA library performed an vivo CRISPR screening orthotopic lung mouse model. Combined with The Cancer Genome Atlas database analysis TLS-related hub genes, found loss Acat1 cells sensitized tumors anti-PD1 treatment, accompanied by increased TME. Mechanistic studies revealed ACAT1 resulted mitochondrial protein hypersuccinylation subsequently enhanced oxidative metabolism, which impeded formation. Elimination ROS NAC or knockdown promoted B cell aggregation construction. Consistently, data from tissue microassays 305 patients cancer showed were more abundant non-small (NSCLC) tissues lower expression. Intratumoral expression was associated poor immunotherapy outcomes NSCLC. In conclusion, our results identified as regulator promising target
Язык: Английский
Процитировано
1
Cancer Science, Год журнала: 2025, Номер unknown
Опубликована: Фев. 25, 2025
ABSTRACT Undifferentiated pleomorphic sarcoma (UPS) has a favorable objective response rate to anti‐PD‐1 drugs compared with other sarcomas. Tertiary lymphoid structure (TLS) is prognostic factor and biomarker for immune checkpoint inhibitors (ICIs). Nevertheless, there are limited data on the tumor microenvironment (TME) support good ICIs in sarcoma. Therefore, this study was conducted investigate impact of TLS prognosis TME. A total 52 UPS wide resection were divided into intratumoral TLS, extratumoral without groups. Survival analysis immunohistochemistry performed evaluate cells molecules, multiplexed immunofluorescence T‐cell exhaustion among three detected 34 cases (65%), including 23 (44%) 11 (21%) cases. Patients had significantly longer overall survival than those (log rank p = 0.020). The group higher number expression PD‐L1 IDO‐1 group. Progenitor‐exhausted T also observed patients UPS. In conclusion, these findings could help predict demonstrated be Intratumoral may ICIs, especially drugs.
Язык: Английский
Процитировано
1
MedComm, Год журнала: 2024, Номер 5(3)
Опубликована: Март 1, 2024
Abstract Cancer is a major cause of death globally, and traditional treatments often have limited efficacy adverse effects. Immunotherapy has shown promise in various malignancies but less effective tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) been associated favorable response to immunotherapy improved survival cancer patients. However, the immunological mechanisms clinical significance TLS malignant are not fully understood. In this review, we elucidate composition, neogenesis, immune characteristics tumors, as well inflammatory development. An in‐depth discussion unique TLSs lung cancer, breast melanoma, soft tissue sarcomas will be presented. Additionally, therapeutic implications TLS, including its role marker prognosis, strategies promote formation maturation explored. Overall, aim provide comprehensive understanding tumor microenvironment suggest potential interventions for treatment.
Язык: Английский
Процитировано
6
Cancer Letters, Год журнала: 2024, Номер 592, С. 216922 - 216922
Опубликована: Май 3, 2024
Язык: Английский
Процитировано
5
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Дек. 4, 2023
The success of immunotherapy approaches, such as immune checkpoint blockade and cellular with genetically modified lymphocytes, has firmly embedded the system in roadmap for combating cancer. Unfortunately, majority cancer patients do not yet benefit from these therapeutic even when prognostic relevance response their tumor entity been demonstrated. Therefore, there is a justified need to explore new strategies inducing anti-tumor immunity. recent connection between formation ectopic lymphoid aggregates at sites patient prognosis, along an effective response, suggests that manipulating occurrence tertiary structures (TLS) may play critical role activating against growing tumor. However, mechanisms governing TLS clear understanding substantial heterogeneity are still lacking. Here, we briefly summarize current state knowledge regarding driving development, outline impact on clinical outcomes patients, discuss appropriate systems modeling help identify protective patients.
Язык: Английский
Процитировано
11
Molecular Biology Reports, Год журнала: 2025, Номер 52(1)
Опубликована: Фев. 4, 2025
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Июнь 4, 2025
Esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), which is the most common subtype in China, one of aggressive gastrointestinal malignancies. Traditional treatments like surgery, radiotherapy, and chemotherapy have limited success, but study tertiary lymphoid structure (TLS) has opened new avenues for immunotherapy. TLS an ectopic immune cluster, including B cells, T dendritic cells (DCs), that forms chronic inflammation such as tumors. often found at tumor invasion margins linked to better prognosis EC patients, with higher density maturation associated prolonged survival. can also serve a biomarker assess immunotherapy outcomes. Further exploration molecular mechanisms could innovate treatments, by inducing formation improve therapy. This review summarizes characteristics EC, clinical findings, limitations directions current research, offering insights future strategies.
Язык: Английский
Процитировано
0
The FASEB Journal, Год журнала: 2024, Номер 38(14)
Опубликована: Июль 17, 2024
G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due their roles in immune cell regulation. Therefore, GPCRs potential targets for cancer immunotherapy. Here, we discuss the current understanding of signaling pathways progression from an immunocellular perspective. Additionally, focus on regulating checkpoint proteins involved evasion. Finally, review progress clinical trials GPCR-targeted drugs treatment, which may be combined with immunotherapy improve treatment efficacy. This expanded role shed light mechanisms underlying provide a novel perspective
Язык: Английский
Процитировано
3