Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors?

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 15, 2025

Abstract In the last two decades, novel and promising cell-based therapies have populated treatment landscape for haematological tumors. However, commonly exploited T NK show limited applicability to solid This is mainly given by impaired tumor trafficking capability effector activity of these cells within a highly immunosuppressive microenvironment. Myeloid spontaneously home tumors can thus be reprogrammed and/or engineered directly attack or locally selectively deliver therapeutically relevant payloads that may improve efficacy immunotherapy against difficult-to-access context myeloid therapies, adoptive transfer monocytes has often been overshadowed infusion differentiated macrophages hematopoietic stem cell transplantation despite their therapeutic potential. Here, we summarize recent improvements benefits using tumors, current clinical applications challenges use as well some possible strategies overcome them.

Language: Английский

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Welche Immuntherapien sind heute schon Standard? Und mit welchen Nebenwirkungen muss man bei Immuntherapien rechnen?

Zentralblatt für Chirurgie - Zeitschrift für Allgemeine Viszeral- Thorax- und Gefäßchirurgie, Journal Year: 2025, Volume and Issue: 150(02), P. 170 - 174

Published: April 1, 2025

Zusammenfassung Im Vergleich zu früheren Behandlungsstandards (einschl. Chemotherapie, Strahlentherapie und Chirurgie) hat die Immuntherapie bedeutende Verbesserungen für Patienten in Bezug auf Überleben Lebensqualität gebracht. ist letztlich eine Art Sammelbegriff Vielzahl unterschiedlichster Therapeutika. Immuntherapeutische Ansätze haben sich fest als ein neuer Pfeiler der Krebsversorgung etabliert, von den neoadjuvanten adjuvanten Ansätzen bis hin zur metastatischen Phase bei diversen Entitäten. In diesem Review-Artikel heben wir hervor, welche Immuntherapien heutzutage onkologischen Versorgung Standard sind, mit einem starken Fokus Immuncheckpoint-Inhibitoren (ICIs), deren Einschränkungen sowie häufig auftretenden Nebenwirkungen.

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Synthetic Gene Circuits as a Promising Approach in Cancer Immunotherapy

Advances in medical diagnosis, treatment, and care (AMDTC) book series, Journal Year: 2024, Volume and Issue: unknown, P. 391 - 418

Published: Aug. 28, 2024

Cancer immunotherapy has emerged as a revolutionary approach in the fight against cancer. Unlike traditional treatments like chemotherapy and radiation, harnesses power of body's own immune system to identify destroy cancer cells. promising therapy, but limitations specificity control hinder its full potential. Synthetic gene circuits offer address these challenges. This chapter emphasizes diverse applications synthetic immunotherapy. Additionally, authors discuss advantages AND gate for minimizing off-target effects, engineered bacteria targeted tumour manipulation, T-cell engineering enhanced anti-tumour activity. Ultimately, therapies are not mutually exclusive. While proven effectiveness accessibility, hold immense promise personalized, long-term solutions.

Language: Английский

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CCR5 and IL-12 co-expression in CAR T cells improves antitumor efficacy by reprogramming tumor microenvironment in solid tumors

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Language: Английский

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LAG3+ CD8+ T cell Subset Boosts Bispecific Antibody Armed Activated T Cell Cytotoxicity Directed at Hormone Receptor+ Breast Cancers

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

ABSTRACT Tumor clearance by T cells is impaired insufficient tumor antigen recognition, infiltration, and the immunosuppressive microenvironment (TME). Although targeted cell therapy circumvents failures in suppression TME failure to infiltrate can hinder these cells. Checkpoint inhibitors (CPI) promises reverse be combined with bispecific antibody armed (BATs) improve clinical outcomes. CPIs require target pathway of inhibition active elicit a therapeutic response. We hypothesize that adoptively transferred function may improved addition CPI if inhibitory functionally active. This study develops kinetic-dynamic model serial killing hormone receptor-positive (HR+) breast cancer mediated BATs using single-cell transcriptomic temporal protein data identify phenotypes quantify receptor expression. LAG3, PD-1, TIGIT were identified as receptors expressed cytotoxic effector CD8 upon exposure HR+ lines. These real-time cytotoxicity multivariate statistical analysis framework predict relevant contributions expressing each reduction. A mechanistic mathematical was developed parametrized expression for silico validation findings analysis. The corroborated predictions which LAG3+ primary effectors, while dampened function. results inform selection combination provide maximize anti-tumor against cancers. Our provides means optimize targets used strategies. What already known on this topic Bispecific therapies are adoptive effectively reroute toward cancerous cells, but lack consistent durable responses. proteins surface activated dampen immune responses overstimulated solid tumors hamper inhibitor drugs response blocking checkpoint signaling only effective microenvironment, highlighting an opportunity enhance BAT efficacy combining treatment synergistic CPI. adds characterizes dynamic, time-resolved patterns cancer-targeting predicts significance high-prevalence It also demonstrates use statistic modeling rational design timing strategies therapies. How might affect research, practice, or policy output justification targeting LAG3 improving patient HER2-/HR+

Language: Английский

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IL-7 Immunotherapies: Current Applications and Engineering Opportunities

Immunological Investigations, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 19

Published: Feb. 21, 2025

IL-7 is a cytokine that plays critical role in the development and proliferation of many different immune cells. notably important for proper activity T cells B Additionally, function natural killer dendritic Because this innate biological activity, has gained traction as potential immunotherapy multiple applications. We conducted comprehensive literature review to explore physiological current applications harnessing biology therapeutic. also investigated ways which being engineered enhance its therapeutic potential. Notably, demonstrated efficacy adoptive cell therapy models vaccine adjuvant. The been used treatment sepsis other chronic infections. To further efficacy, by fusing antibody fragments or bioactive targeting molecules. These therapeutics seek improve cytokine's pharmacokinetic immunological properties reduce off-target effects. immunotherapies largely remain at preclinical stage, but there growing interest IL-7's increasing opportunities engineer molecule future clinical translation.

Language: Английский

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Screening and mechanistic study of natural compounds that enhance T cell anti-tumor effects post-heat treatment

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction Following the approval of Chimeric Antigen Receptor T-cell Immunotherapy(CAR-T) in multiple countries, Food and Drug Administration (FDA) approved tumor-infiltrating lymphocytes (TILs) receptor-engineered T cells (TCR-T) treatments this year. The utilization adoptive immunotherapy tumor treatment has become increasingly prominent. Optimizing cytotoxic effects immune under vitro culture conditions represents a current hot research topic domain. Methods In experiment, we conducted heat on Jurkat-derived at 39°C. On basis, utilized nine distinct injectable solutions over 70 monomer components Traditional Chinese Medicine (TCM). Subsequently, co-cultured these treated Jurkat with K562-eGFP cells, co-culture process was monitored real-time using IncuCyte live-cell analysis system. Equally important, combined HiMAP high-throughput transcriptome sequencing, proteomics, metabolomics for in-depth examination. We screened compounds possessing anti-tumor properties thoroughly investigated their mechanisms action. Results Discussion findings indicated that heating augmented effect against malignant tumors, optimal achieved when were exposed to 39°C duration 24 hours(48% increase cell proliferation rate compared 37°C treatment). By triggering generation shock proteins facilitating mitochondrial energy supply, amplified functions cells. analyzing data, identified 3 more than 20 effective monomers capable further enhancing tumor-killing ability High-throughput transcriptomics studies disclosed combination thermotherapy TCM promoted proliferation, activation, thereby activating Regulation mitotic cycle exert effects. integration transcriptomic proteomic data demonstrated Shengmai Injection significantly enhances by down-regulating Apoptosis signaling pathways.

Language: Английский

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Dual modulation of cytotoxic and checkpoint receptors tunes the efficacy of adoptive Delta One T cell therapy against colorectal cancer

Nature Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

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Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Hepatocellular carcinoma stands as one of the foremost contributors to cancer-associated fatalities globally, and limitations traditional treatment methods have prompted researchers explore new therapeutic options. Recently, cell therapy has emerged a promising approach for HCC, showing significant potential in improving patient outcomes. This review article explores use covering different types, mechanisms behind their effectiveness, recent advancements clinical trials, ongoing challenges. aims provide insightful perspectives future research applications treating HCC by synthesizing current knowledge.

Language: Английский

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