Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

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Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216894 - 216894

Published: April 16, 2024

This comprehensive review delves into the pivotal role of tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights intricate interplay between cells their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular acellular elements, not only fosters progression but also profoundly affects efficacy conventional emerging therapies. Through nuanced exploration, this illuminates multifaceted nature elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, establishment physical barriers delivery. Moreover, it investigates innovative approaches aimed at targeting including stromal reprogramming, modulation, extracellular matrix (ECM)-targeting agents, personalized medicine strategies, highlighting potential augment treatment outcomes. Furthermore, critically evaluates challenges posed by complexity heterogeneity which contribute variable responses potentially unintended consequences. underscores need identify robust biomarkers advance predictive models anticipate outcomes, well advocate for combination therapies that address multiple facets TME. Finally, emphasizes necessity an interdisciplinary approach integration cutting-edge technologies unravel intricacies thereby facilitating development more effective, adaptable, treatments. By providing critical current state TME research implications future oncology, highlights evolving landscape field.

Language: Английский

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Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(30)

Published: Aug. 21, 2023

The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T activity in the tumor microenvironment. While clinical approaches to inhibiting PD-1 using antibody blockade have been broadly successful, these lead widespread suppression, increasing risk autoimmune reactions. This study reports development an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient knockdown cells. In developing this platform, interesting interactions are observed between two cargoes when co-encapsulated, leading improved characteristics compared delivering either cargo alone. messenger (mRNA)/small interfering (siRNA) co-delivery adopted deliver chimeric antigen receptor (CAR) mRNA siRNA targeting primary human cells ex vivo strong CAR without apparent changes overall activation state. delivery shows great promise immune modulation number immunoengineering applications, including cancer immunotherapies.

Language: Английский

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Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 390(22), P. 2074 - 2082

Published: June 12, 2024

Indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed presence gene product tumor cells. Whole-genome samples and peripheral blood identified single lentiviral insertion site within second intron

Language: Английский

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CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

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CAR-NK cells for cancer immunotherapy: recent advances and future directions

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

Published: Feb. 9, 2024

Natural Killer (NK) cells, intrinsic to the innate immune system, are pivotal in combating cancer due their independent cytotoxic capabilities antitumor response. Unlike predominant treatments that target T cell immunity, limited success of immunotherapy emphasizes urgency for innovative approaches, with a spotlight on harnessing potential NK cells. Despite tumors adapting mechanisms evade cell-induced cytotoxicity, there is optimism surrounding Chimeric Antigen Receptor (CAR) This comprehensive review delves into foundational features and recent breakthroughs comprehending dynamics cells within tumor microenvironment. It critically evaluates applications challenges associated emerging CAR-NK therapeutic strategies, positioning them as promising tools evolving landscape precision medicine. As research progresses, unique attributes offer new avenue interventions, paving way more effective precise approach treatment.

Language: Английский

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Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

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New insights into the role of macrophages in cancer immunotherapy

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

Published: March 28, 2024

Macrophages are the main component of tumor microenvironment, which differentiated from monocytes in blood and play an important role cancer development. Tumor-associated macrophages (TAMs) can promote growth, invasion, metastasis, resistance to anti–programmed death receptor 1 therapy by regulating programmed cell ligand expression interacting with other immune cells microenvironment. However, when activated properly, also anti-tumor enhancing phagocytosis cytotoxicity cells. TAM is associated poor prognosis drug patients treated immunotherapy, indicating that attractive targets for combined treatment. Combination targeting TAMs immunotherapy overcomes achieved excellent results some cancers, may be a promising strategy treatment future. Herein, we review recent findings on development, immunotherapy. We focus mainly macrophage-centered therapy, including strategies deplete reprogram TAMs, represent potential improving efficacy.

Language: Английский

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CAR‑T cell therapy: A breakthrough in traditional cancer treatment strategies (Review)

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(3)

Published: Jan. 23, 2024

Chimeric antigen receptor (CAR)‑T cell therapy is an innovative approach to immune that works by modifying the T cells of a patient express CAR protein on their surface, and thus induce recognition destruction cancer cells. CAR‑T has shown some success in treating hematological tumors, but it still faces number challenges treatment solid such as selection, tolerability safety. In response these issues, studies continue improve design pursuit improved therapeutic efficacy future, expected become important treatment, may provide new ideas strategies for individualized immunotherapy. The present review provides comprehensive overview principles, clinical applications, therapy.

Language: Английский

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The Progress and Prospects of Immune Cell Therapy for the Treatment of Cancer

Cell Transplantation, Journal Year: 2024, Volume and Issue: 33

Published: Jan. 1, 2024

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is specialized form of immunotherapy that utilizes living immune cells therapeutic reagents for the cancer. Unlike traditional drugs, therapies are considered “living drugs,” and these products currently customized require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T have received tremendous attention in industry regarding hematologic malignancies, their effectiveness treating solid tumors often restricted, leading to emergence alternative therapies. Tumor-infiltrating lymphocytes (TIL) therapy, cytokine-induced killer (CIK) dendritic (DC) vaccines, DC/CIK designed use body’s natural defense mechanisms target eliminate cells, usually fewer side effects or risks. On other hand, therapies, such receptor-T (CAR-T) cell, T (TCR)-T, receptor-natural (CAR-NK), CAR-macrophages (CAR-M) typically utilize either autologous stem allogeneic xenogeneic genetically modified which higher levels manipulation high risk. These high-risk hold special characteristics tumor targeting signal transduction, triggering new anti-tumor responses. Recently, significant advances been achieved both basic clinical researches on mechanisms, product designs, technological innovations. With swift integration innovation landscape, key future development directions emerged. To meet demands advancements cancer, we comprehensively systematically investigate progress this study. Based methodological features analyzed main technical advantages transformation risks associated with We also forecasted application prospects, providing references relevant enterprises necessary information make informed decisions R&D direction selection.

Language: Английский

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