Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

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

Published: May 13, 2024

CD4 + CD25 Foxp3 regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining homeostasis and preventing excessive responses. This review explores signaling pathways cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, IL-35, which foster differentiation enhance immunosuppressive capabilities Tregs. It also examines how, conversely, signals mediated by IL-6 tumor necrosis -alpha (TNF-α) can undermine suppressive functions or even drive their reprogramming into effector cells. The B7 family comprises indispensable co-stimulators cell activation. Among its members, this focuses on capacity CTLA-4 PD-1 to differentiation, function, survival As Tregs play an essential role in homeostasis, dysfunction contributes pathogenesis autoimmune diseases. delves potential employing Treg-based immunotherapy treatment diseases, transplant rejection, cancer. By shedding light these topics, article aims our understanding regulation therapeutic various pathological conditions.

Language: Английский

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The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 12, 2024

Abstract The programmed cell death 1 (PD-1) signaling pathway, a key player in immune checkpoint regulation, has become focal point cancer immunotherapy. In the context of cancer, upregulated PD-L1 on tumor cells can result T exhaustion and evasion, fostering progression. advent PD-1/PD-L1 inhibitor demonstrated clinical success by unleashing from exhaustion. Nevertheless, challenges such as resistance adverse effects have spurred exploration innovative strategies, with bispecific antibodies (BsAbs) emerging promising frontier. BsAbs offer multifaceted approach to immunotherapy simultaneously targeting other regulatory molecules. We focus recent advancements therapy particular emphasis development potential BsAbs, especially solid tumors. Various BsAb products PD-1 are discussed, highlighting their unique mechanisms action therapeutic potential. Noteworthy examples include anti-TGFβ × PD-L1, anti-CD47 anti-VEGF anti-4-1BB anti-LAG-3 anti-PD-1 CTLA-4 BsAbs. Besides, we summarize ongoing studies evaluating efficacy safety these agents. By unraveling intricacies microenvironment harnessing synergistic anti-PD-1/PD-L1 there exists elevate precision immunotherapy, ultimately enabling personalized treatment strategies tailored individual patient profiles.

Language: Английский

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PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications

Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 102(8), P. 987 - 1000

Published: June 27, 2024

Language: Английский

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Expanding the Potential of Circular RNA (CircRNA) Vaccines: A Promising Therapeutic Approach

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 379 - 379

Published: Jan. 4, 2025

In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, an RNA offers advantages in preventing infectious diseases by serving a vector protein expression through non-canonical translation. Notably, vaccines demonstrated enduring antigenic generate larger percentage of neutralizing antibodies compared mRNA administered at the same dosage. Furthermore, can elicit robust cellular humoral immunity, indicating potential tumor vaccine development. However, certain challenges must be addressed facilitate widespread use both disease prevention treatment. These include low efficiency linear circularization, suboptimal targeting delivery systems, assessment side effects. This work aims describe characteristics functions circRNAs, elucidate mechanism behind vaccines, discuss applications treatment tumors, along with future applications.

Language: Английский

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Anti-PD-L1-Based Bispecific Antibodies Targeting Co-Inhibitory and Co-Stimulatory Molecules for Cancer Immunotherapy

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 454 - 454

Published: Jan. 17, 2024

Targeting PD-L1 via monospecific antibodies has shown durable clinical benefits and long-term remissions where patients exhibit no cancer signs for many years after treatment. However, the by anti-PD-L1 monotherapy have been limited to a small fraction of with certain types. bispecific (referred as anti-PD-L1-based bsAbs) which can simultaneously bind both co-inhibitory co-stimulatory molecules may increase antitumor responses in who would not benefit from monotherapy. A growing number bsAbs developed fight against this deadly disease. This review summarizes recent advances immunotherapy patents literatures, discusses their anti-tumor efficacies vitro vivo. Over 50 targeting investigated biological testing or trials since 2017. At least eleven proteins, such CTLA-4, LAG-3, PD-1, PD-L2, TIM-3, TIGIT, CD28, CD27, OX40, CD137, ICOS, are involved these investigations. Twenty-two being evaluated treat various advanced cancers trials, wherein indications include NSCLC, SNSCLC, SCLC, PDA, MBNHL, SCCHN, UC, EC, TNBC, CC, some other malignancies. The released data indicated that most were well-tolerated showed promising efficacy solid tumors. approved investigational much more significant adverse reactions compared antibodies, be further optimized molecular structure modification avoid reduce reactions.

Language: Английский

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Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1237 - 1237

Published: March 21, 2024

During the last decade, we have witnessed several milestones in treatment of various resistant cancers including immunotherapeutic strategies that proven to be superior conventional options, such as chemotherapy and radiation. This approach utilizes host’s immune response, which is triggered by cancer cells expressing tumor-associated antigens or neoantigens. The responsive cytotoxic CD8+ T specifically target kill tumor cells, leading regression prolongation survival some cancers; however, may exhibit resistance due inactivation anti-tumor cells. One mechanism become dysfunctional through activation inhibitory receptor programmed death-1 (PD-1) corresponding (or other microenvironment (TME)) express death ligand-1 (PD-L1). Hence, blocking PD-1/PD-L1 interaction via specific monoclonal antibodies (mAbs) restores cells’ functions, regression. Accordingly, Food Drug Administration (FDA) has approved checkpoint act inhibitors. Their clinical use cancers, metastatic melanoma non-small-cell lung (NSCLC), shown significant responses. We investigated an alternative prevent expression PD-L1 on targeting oncogenic transcription factor Yin Yang 1 (YY1), a known overexpressed many cancers. report regulation YY1 at transcriptional, post-transcriptional, post-translational levels, resulting restoration functions. performed bioinformatic analyses further explore relationship between both corroborate these findings. In addition its PD-L1, anti-cancer activities, proliferation cell viability, invasion, epithelial–mesenchymal transition (EMT), metastasis, chemo-immuno-resistance. Thus, will multitude activities obliteration activities. Various are proposed selectively human present promising novel therapeutic for treating unresponsive phenotypes. These findings underscore distinct regulatory roles (CD274) progression response.

Language: Английский

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Treatment-related adverse events of immune checkpoint inhibitors in clinical trials: a systematic review and meta-analysis

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: May 17, 2024

Aim This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites. Methods We systematically searched PubMed, Embase, Cochrane databases for trials investigating ICI-based published between their inception August 2023. Results In total, 147 studies involving 45,855 patients met inclusion criteria. Among them, treated with ICIs reported 39.8% 14.9% all-grade grade ≥3 immune-related (irAEs), respectively. The most common irAEs were dermatological gastrointestinal issues, diarrhea, pruritus, whereas who received showed irAEs, including events, increased aspartate aminotransferase alanine transaminase levels, hepatic events. overall trAE in was 83.2% trAEs 38.2% trAEs. TrAE highest cytotoxic T lymphocyte antigen-4 inhibitors trAEs, incidences 86.4% 39.2%, combined targeted therapy 96.3% 59.4%, anemia, decrease white blood cell count, neutrophil nausea, fatigue, alopecia; presented relatively high Conclusion provided comprehensive data regarding receiving ICIs. These results should be applied clinical practice to provide an essential reference safety Systematic review registration INPLASY platform, identifier INPLASY202380119.

Language: Английский

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Treatment-related Adverse Events, Including Fatal Toxicities, in Patients With Extensive-stage Small-cell Lung Cancer Receiving Adjuvant Programmed Cell Death 1/Programmed Cell Death Ligand 1 Inhibitors: A Meta-analysis and Trial Sequential Analysis of Randomized Controlled Trials

Clinical Oncology, Journal Year: 2024, Volume and Issue: 36(10), P. e408 - e419

Published: July 2, 2024

Language: Английский

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Systematic Review on the Effectiveness and Outcomes of Nivolumab Treatment Schemes in Advanced and Metastatic Cervical Cancer

Diseases, Journal Year: 2024, Volume and Issue: 12(4), P. 77 - 77

Published: April 15, 2024

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging potential therapeutic option. This systematic review rigorously assesses effectiveness outcomes of various treatment regimens within this patient cohort, drawing from clinical trials real-world evidence up to December 2023. Following comprehensive search across PubMed, Scopus, Embase, four studies were deemed eligible, involving collective total 80 patients. One preliminary trial data excluded final analysis, well other proceedings abstracts on efficacy safety advanced cancer. The patients’ average age these was 48 years, an 38% having Eastern Cooperative Oncology Group (ECOG) performance status 1. Notably, 64% all patients positive for high-risk HPV, 71% exhibited PD-L1 positivity, indicating substantial target population nivolumab. analysis revealed pooled objective response rate (ORR) 48%, disease control (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months observed 50%, reflecting significant managing stages disease. highlights influence rates underscores enhanced associated combination therapy approaches. By delineating variability pinpointing key factors affecting survival, calls further investigations refine nivolumab’s application, aiming improve

Language: Английский

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Triple-negative breast cancer: from none to multiple therapeutic targets in two decades

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 9, 2023

Triple-negative breast cancers (TNBCs) are more likely to occur in younger patients and have a poor prognosis. They highly heterogeneous tumors consisting of different molecular subtypes. The only common characteristic among them is the absence targets for endocrine therapy human epidermal growth factor receptor 2 (HER2) blockade. In past two decades, there has been an increased understanding these from perspective, leading their stratification according new therapeutic strategies. TNBC ushered carcinomas into era immunotherapy. higher frequency germline BRCA mutations enables targeting this repair defect by drugs like PARP inhibitors, resulting synthetic lethality neoplastic cells. Additionally, we identification molecules which generation smart drugs, such as antibody-drug conjugates (ADCs), directed. review, will discuss trajectory knowledge systematic manner, presenting bases, possibilities, biomarkers.

Language: Английский

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