Cold and hot tumors: from molecular mechanisms to targeted therapy

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

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Emerging biomaterials for tumor immunotherapy

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cells; however, these interactions also lead to malignancy. There has been a dramatic increase application immunotherapy last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute play an important role treatment, making it research hotspot biomedical field. This review discusses immunotherapies development related for first summarizes types tumor applicable clinical practice as well their underlying mechanisms. Further, focuses on applied metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer cell membrane nanocarriers. Moreover, we introduce preparation processing technologies (liposomes, microspheres, microneedles, hydrogels) summarize mechanisms when immunotherapy. Finally, discuss future advancements shortcomings Research biomaterial-based is booming; several challenges remain be overcome transition experimental Biomaterials have optimized continuously nanotechnology achieved continuous progression, ensuring more efficient biomaterials, thereby providing platform opportunity breakthroughs

Language: Английский

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Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 18, 2024

The potential of immune checkpoint inhibitors (ICI) may be limited in situations where cell fitness is impaired. Here, we show that the efficacy cancer immunotherapies compromised by accumulation senescent cells mice and context therapy-induced senescence (TIS). Resistance to immunotherapy associated with a decrease activation CD8 T within tumors. Elimination restores homeostasis tumor micro-environment (TME) increases survival response immunotherapy. Using single-cell transcriptomic analysis, observe injection ABT263 (Navitoclax) reverses exacerbated immunosuppressive profile myeloid TME. these also proliferation vitro abrogates resistance vivo. Overall, our study suggests use senolytic drugs before ICI constitute pharmacological approach improve effectiveness immunotherapies.

Language: Английский

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TME-Related Biomimetic Strategies Against Cancer

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 109 - 135

Published: Jan. 1, 2024

Abstract: The tumor microenvironment (TME) plays an important role in various stages of generation, metastasis, and evasion immune monitoring treatment. TME targeted therapy is based on components, related pathways or active molecules as therapeutic targets. Therefore, environmental differences between normal cells has been widely studied. Biomimetic nanocarriers with low clearance, immunogenicity, high targeting have enormous potential This review introduces the composition characteristics TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), blood vessels, non-tumor cells, latest research progress biomimetic nanoparticles (NPs) TME. It also discusses opportunities challenges clinical transformation nanoparticles. Keywords: nanoparticles, delivery system, therapy, cell membrane-coating

Language: Английский

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Radiotherapy and immunology

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(7)

Published: May 21, 2024

The majority of cancer patients receive radiotherapy during the course treatment, delivered with curative intent for local tumor control or as part a multimodality regimen aimed at eliminating distant metastasis. A major focus research has been DNA damage; however, in past two decades, emphasis shifted to important role immune system plays radiotherapy-induced anti-tumor effects. Radiotherapy reprograms microenvironment, triggering and RNA sensing cascades that activate innate immunity ultimately enhance adaptive immunity. In opposition, also induces suppression immunity, including recruitment regulatory T cells, myeloid-derived suppressor suppressive macrophages. balance pro- is regulated by chemokines cytokines. Microbiota can influence outcomes under clinical investigation. Blockade PD-1/PD-L1 axis CTLA-4 extensively investigated combination radiotherapy; we include review trials involving inhibition these checkpoints radiotherapy.

Language: Английский

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