Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 367, P. 500 - 514
Published: Feb. 3, 2024
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2052 - 2078
Published: April 1, 2024
Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense respond with targeted precision to perturbations induced pathogens tissue damage. Here, we review key principles underlying adaptive orchestrated distinct T cell B populations their extensions disease therapies. We discuss the intracellular intercellular processes shaping antigen specificity recognition in immune activation lymphocyte functions mediating effector memory responses. also describe how balance protective autoimmunity immunopathology, including during tolerance, response chronic stimulation, adaptation non-lymphoid tissues coordinating homeostasis. Finally, extracellular signals cell-intrinsic programs underpinning conclude summarizing advances vaccination engineering responses for therapeutic interventions. A deeper understanding of these holds promise uncovering new means improve human health.
Language: Английский
Citations
65
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 338 - 357
Published: March 1, 2024
SummaryOver the past decade, RAS oncogenic proteins have transitioned from being deemed undruggable to having two clinically approved drugs, with several more in advanced stages of development. Despite initial benefit KRAS-G12C inhibitors for patients tumors harboring this mutation, rapid emergence drug resistance underscores urgent need synergize these other therapeutic approaches improve outcomes. mutant tumor cells can create an immunosuppressive microenvironment (TME), suggesting increased susceptibility immunotherapies following inhibition. This provides a rationale combining inhibitory drugs immune checkpoint blockade (ICB). However, achieving synergy clinical setting has proven challenging. Here, we explore how understanding impact on TME guide innovative inhibition immunotherapies, review progress both pre-clinical and stages, discuss challenges future directions.
Language: Английский
Citations
50
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)
Published: Feb. 1, 2024
Abstract Although immunotherapy has made breakthrough progress, its efficacy in solid tumours remains unsatisfactory. Exosomes are the main type of extracellular vesicles that can deliver various intracellular molecules to adjacent or distant cells and organs, mediating biological functions. Studies have found exosomes both activate immune system inhibit system. The antigen major histocompatibility complex (MHC) carried make it possible develop them as anticancer vaccines. derived from blood, urine, saliva cerebrospinal fluid be used ideal biomarkers cancer diagnosis prognosis. In recent years, exosome-based therapy great progress fields drug transportation immunotherapy. Here, we review composition sources microenvironment further elaborate on potential mechanisms pathways by which influence for cancers. Moreover, summarize clinical application prospects engineered exosome vaccines Eventually, these findings may open up avenues determining diagnosis, treatment, prognosis
Language: Английский
Citations
45
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1415 - 1433.e12
Published: July 18, 2024
Language: Английский
Citations
23
Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)
Published: Aug. 1, 2024
Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.
Language: Английский
Citations
22
Cell, Journal Year: 2024, Volume and Issue: 187(18), P. 4905 - 4925.e24
Published: July 5, 2024
Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on microenvironment (TME) remains elusive. Our study generates single-cell gene expression T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy PARP inhibitor (PARPi) niraparib achieves impressive 62.5% 73.6% response rates per RECIST v.1.1 GCIG CA125, respectively. We identify effector regulatory (eTregs) as key responders neoadjuvant therapies, co-occurring other tumor-reactive cells, particularly terminally exhausted CD8+ (Tex). TME-wide interferon signaling correlates upregulating MHC class co-inhibitory ligands, potentially driving Treg Tex fates. Depleting eTregs mouse models, or without inhibition, significantly suppresses growth observable toxicities, underscoring potential eTreg-focused therapeutics for HGSOC HRD-related tumors.
Language: Английский
Citations
21
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: Nov. 8, 2024
Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group lymphocytes with ability to suppress responses and maintain homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity facilitate cancer progression by weakening functions effector (Teffs). Consequently, targeting eliminate them from tumor microenvironments improve Teffs' activity could emerge as effective strategy for immunotherapy. This review outlines biology Tregs, detailing their origins, classification, crucial markers. Our focus lies on complex role in cancer's development, treatment, particularly suppressive upon via multiple mechanisms. We delve into Tregs' involvement checkpoint blockade (ICB) therapy, dual effect immunotherapy potential biomarkers ICB therapy effectiveness. also summarize advances therapies adjust optimize which be devising innovative treatment strategies.
Language: Английский
Citations
19
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: March 13, 2024
Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding transformation to 'hot' is essential developing effective cancer treatments. Furthermore, tumor profiling critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success immunotherapy relies on T cells' ability recognize eliminate cells. In absence cell infiltration leads ineffectiveness ICI therapy. Addressing these challenges, especially impairment activation homing, crucial enhance therapy's efficacy. Concurrently, strategies convert into ones, including boosting adoptive therapies such as cell-recruiting bispecific antibodies Chimeric Antigen Receptor (CAR) cells, are under extensive exploration. Thus, identifying key factors that impact vital creating treatments targeting tumors.
Language: Английский
Citations
17
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189259 - 189259
Published: Jan. 1, 2025
As immunosuppressive cells, Regulatory T cells (Tregs) exert their influence on tumor immune escape within the microenvironment (TME) by effectively suppressing activity of other thereby significantly impeding anti-tumor response. In recent years, metabolic characteristics Tregs have become a focus research, especially important role lipid metabolism in maintaining function Tregs. Consequently, targeted interventions aimed at modulating been recognized as an innovative and promising approach to enhance effectiveness immunotherapy. This review presents comprehensive overview pivotal regulating Tregs, with specific targeting augment responses. Furthermore, we discuss potential opportunities challenges associated this strategy, aiming provide novel insights for enhancing efficacy cancer
Language: Английский
Citations
4
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113952 - 113952
Published: Jan. 6, 2025
Regulatory T (Treg) cells, immunosuppressive CD4+ can impede anti-tumor immunity, complicating cancer treatment. Since their discovery, numerous studies have been dedicated to understand Treg cell biology, with a focus on checkpoint pathways' role in generation and function. Immune checkpoints, such as PD-1/PD-L1, CTLA-4, TIGIT, TIM-3, OX40, are pivotal controlling expansion activity the tumor microenvironment (TME), affecting ability suppress immune responses. This review examines complex relationship between these checkpoints Tregs TME, how they influence immunity. We also discuss therapeutic potential of targeting enhance including use blockade (ICB) therapies novel approaches CCR8-targeted therapies. Understanding interaction cells lead more effective immunotherapeutic strategies, combining inhibitors, improve patient outcomes
Language: Английский
Citations
2