Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics

Nature Reviews Clinical Oncology, Год журнала: 2022, Номер 19(5), С. 287 - 305

Опубликована: Фев. 7, 2022

Язык: Английский

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Role of tumor microenvironment in cancer progression and therapeutic strategy

Cancer Medicine, Год журнала: 2023, Номер 12(10), С. 11149 - 11165

Опубликована: Фев. 21, 2023

Abstract Cancer is now considered a tumor microenvironment (TME) disease, although it was originally thought to be cell and gene expression disorder. Over the past 20 years, significant advances have been made in understanding complexity of TME its impact on responses various anticancer therapies, including immunotherapies. immunotherapy can recognize kill cancer cells by regulating body's immune system. It has achieved good therapeutic effects solid tumors hematological malignancies. Recently, blocking programmed death‐1 (PD‐1), ligand‐1 (PD‐L1), death Ligand‐2 (PD‐L2), construction antigen chimeric T (CAR‐T) vaccines become popular immunotherapies Tumorigenesis, progression, metastasis are closely related TME. Therefore, we review characteristics molecules TME, interaction between PD‐1 promising therapeutics.

Язык: Английский

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Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июль 7, 2023

Abstract Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells recognize attack are isolated from patients modified tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large lymphoma, multiple myeloma by targeting CD-19 maturation Bi-specific chimeric receptors may contribute mitigating escape, but their efficacy could be limited in cases where certain cells do not express targeted Despite success cancers, technology faces challenges solid tumors, including lack of reliable antigens, hypoxic cores, immunosuppressive environments, enhanced reactive oxygen species, decreased T-cell infiltration. To overcome these challenges, current research aims identify antigens develop cost-effective, microenvironment-specific This review covers evolution against various hematological highlights faced suggests strategies obstacles, such as utilizing single-cell RNA sequencing artificial intelligence optimize clinical-grade

Язык: Английский

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Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Фев. 21, 2023

Abstract Ongoing research has revealed that the existence of cancer stem cells (CSCs) is one biggest obstacles in current therapy. CSCs make an influential function tumor progression, recurrence and chemoresistance due to their typical stemness characteristics. are preferentially distributed niches, those niche sites exhibit characteristics microenvironment (TME). The complex interactions between TME illustrate these synergistic effects. phenotypic heterogeneity within spatial with surrounding led increased therapeutic challenges. interact immune protect themselves against clearance by exploiting immunosuppressive multiple checkpoint molecules. also can surveillance excreting extracellular vesicles (EVs), growth factors, metabolites cytokines into TME, thereby modulating composition TME. Therefore, being considered for development anti-tumor agents. We discuss here molecular mechanisms comprehensively review interplay system. Thus, studies on this topic seem provide novel ideas reinvigorating approaches cancer.

Язык: Английский

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Hot and cold tumors: Immunological features and the therapeutic strategies

MedComm, Год журнала: 2023, Номер 4(5)

Опубликована: Авг. 26, 2023

Abstract The “hotness” or “coldness” of the tumors are determined by information cancer cells themselves, tumor immune characteristics, microenvironment, and signaling mechanisms, which key factors affecting patients’ clinical efficacy. switch mechanism its corresponding pathological characteristics treatment strategies frontier hot spot treatment. How to distinguish effectively clarify causes, microenvironment state, very important for response efficacy treatments. Starting from concept cold tumor, this review systematically summarized molecular influencing factors, therapeutic “hot tumors,” analyzed immunophenotypes, pathways, markers that contribute tumors” in details. Different “cold based on were with drug targets proteins tumors.” Furthermore, combines different traditional medicine modern medicine, provide a basis guidance decision‐making

Язык: Английский

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PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 1, 2023

PD-1 (Programmed Cell Death Protein-1) and PD-L1 Ligand-1) play a crucial role in regulating the immune system preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape detection promote tumor growth. Therapies targeting PD-1/PD-L1 pathway have transformed cancer treatment demonstrated significant effectiveness against various types. This study delves into structure signaling dynamics of its ligands PD-L1/PD-L2, diverse inhibitors their efficacy, resistance observed some patients. Furthermore, explored challenges associated with inhibitor approach. Recent advancements combination immunotherapy chemotherapy, radiation, surgical procedures enhance patient outcomes also been highlighted. Overall, offers an in-depth overview significance future implications oncology.

Язык: Английский

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Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 10, 2024

The programmed death-1 receptor (PD-1) acts as a T-cell brake, and its interaction with ligand-1 (PD-L-1) interferes signal transduction of the receptor. This leads to suppression survival, proliferation, activity in tumor microenvironment resulting compromised anticancer immunity. PD-1/PD-L-1 blockade shown remarkable clinical success various cancer immunotherapies. To date, most blockers approved for use are monoclonal antibodies (mAbs); however, their therapeutic limited owing poor responses proportion patients. mAbs also displayed low penetration, steep production costs, incidences immune-related side effects. strongly indicates importance developing novel inhibitors immunotherapeutic agents. Recently, advancements small molecule-based (SMIs) that directly block axis gained attention from scientific community involved research. SMIs demonstrated certain advantages over mAbs, including longer half-lives, cost, greater cell possibility oral administration. Currently, several development pipeline potential therapeutics immunotherapy. develop new SMIs, wide range structural scaffolds have been explored excellent outcomes; biphenyl-based studied. In this review, we analyzed targeting treatment. Altogether, present review delves into problems related detailed discussion on current status SMIs. article may provide comprehensive guide medicinal chemists regarding required inhibition.

Язык: Английский

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Small molecule-based immunomodulators for cancer therapy

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 12(12), С. 4287 - 4308

Опубликована: Ноя. 12, 2022

Immunotherapy has led to a paradigm shift in the treatment of cancer. Current cancer immunotherapies are mostly antibody-based, thus possessing advantages regard pharmacodynamics (e.g., specificity and efficacy). However, they have limitations terms pharmacokinetics including long half-lives, poor tissue/tumor penetration, little/no oral bioavailability. In addition, therapeutic antibodies immunogenic, may cause unwanted adverse effects. Therefore, researchers shifted their efforts towards development small molecule-based immunotherapy, as molecules overcome above disadvantages associated with antibodies. Further, immunomodulators complementary modalities for treatment, be combined elicit synergistic Recent years witnessed rapid immunotherapy. this review, we describe current progress (inhibitors/agonists/degraders) therapy, those targeting PD-1/PD-L1, chemokine receptors, stimulator interferon genes (STING), Toll-like receptor (TLR), etc. The tumorigenesis mechanism various targets respective modulators that entered clinical trials also summarized.

Язык: Английский

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Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

Military Medical Research, Год журнала: 2023, Номер 10(1)

Опубликована: Апрель 28, 2023

Immune checkpoint blockade (ICB) therapy for cancer has achieved great success both in clinical results and on the market. At same time, drives more attention from scientists to improve it. However, only a small portion of patients are responsive this therapy, it comes with unique spectrum side effects termed immune-related adverse events (irAEs). The use nanotechnology could ICBs' delivery tumor, assist them penetrating deeper into tumor tissues alleviate their irAEs. Liposomal nanomedicine been investigated used decades, is well-recognized as most successful nano-drug system. combination ICB liposomal help efficacy therapy. In review, we highlighted recent studies using (including new emerging exosomes inspired nano-vesicles) associating

Язык: Английский

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Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2769 - 2769

Опубликована: Фев. 1, 2023

Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy become the standard care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, mechanism action immune exposes new toxicity profile known immune-related adverse effects (irAEs). This novel can damage any organ, but skin, digestive and endocrine systems are most frequently afflicted. Most ICI-attributed symptoms mild, some severe necessitate multidisciplinary side effect Obtaining knowledge on various forms toxicities swiftly changing treatment techniques to lower probability experiencing irAEs has priority oncological care. In recent years, there been growing understanding an intriguing link between gut microbiome ICI outcomes. Multiple studies demonstrated connection microbial metagenomic metatranscriptomic patterns efficacy malignant melanoma, lung colorectal cancer. The immunomodulatory real biological background well. Furthermore, specific signatures metabolites might be associated with onset severity symptoms. By identifying these factors, biomarkers used clinical practice predict manage potential irAEs. comprehensive review aims summarize aspects ICI-related their association metabolome. We aim explore current state important reliable irAE-related origin discuss toxicity.

Язык: Английский

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