Hot and cold tumors: Immunological features and the therapeutic strategies

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Aug. 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

Language: Английский

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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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Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Language: Английский

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Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

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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Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6810 - 6821

Published: April 13, 2024

Anti-PD-L1 immunotherapy, a new lung cancer treatment, is limited to few patients due low PD-L1 expression and tumor immunosuppression. To address these challenges, the upregulation of has potential elevate response rate efficiency anti-PD-L1 alleviate immunosuppression microenvironment. Herein, we developed novel usnic acid-derived Iridium(III) complex, Ir-UA, that boosts converts "cold tumors" "hot". Subsequently, administered Ir-UA combined with in mice, which effectively inhibited growth promoted CD4+ CD8+ T cell infiltration. our knowledge, first iridium-based complex stimulate by explicitly regulating its transcription factors, not only provides promising platform for immune checkpoint blockade but, more importantly, an effective treatment strategy expression.

Language: Английский

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State-Of-The-Art Advancements on Cancer Vaccines and Biomarkers

American Society of Clinical Oncology Educational Book, Journal Year: 2024, Volume and Issue: 44(3)

Published: April 26, 2024

The origins of cancer vaccines date back to the 1800s. Since then, there have been significant efforts generate against solid and hematologic malignancies using a variety platforms. To date, these generally met with minimal success. However, in era improved methods technological advancements, supported by compelling preclinical clinical data, wave renewed interest field offers promise discovering field-changing paradigms management established resected disease vaccines. These include novel approaches personalized neoantigen vaccine development, as well innovative immune-modulatory (IMVs) that facilitate activation antiregulatory T cells limit immunosuppression caused regulatory immune cells. This article will introduce some limitations affected development over past several decades, followed an introduction latest advancements IMV therapy, then conclude discussion newest technologies progress are occurring across space. Cancer among most promising frontiers for breakthrough innovations strategies poised make measurable impact ongoing fight cancer.

Language: Английский

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Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer

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

Published: Jan. 3, 2025

ErbB3 is markedly overexpressed in breast cancer cells and associated with resistance metastasis. Additionally, expression levels are positively correlated low densities of tumor-infiltrating lymphocytes, a marker poor prognosis. Consequently, promising therapeutic target for immunotherapy. Here, we report the generation ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) by transducing cord blood-derived primary NK using vsv-g envelope-pseudotyped lentiviral vectors. Transduced displayed stable CAR-expressing activity increased cytotoxicity against ErbB3-positive cell lines. Furthermore, anti-ErbB3 (aErbB3) CAR-NK strongly reduced tumor burden SK-BR-3 xenograft mouse model without observable side effects. These findings underscore potential aErbB3 as targeted immunotherapy cancer, suggesting alternative to conventional treatments.

Language: Английский

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Molecular Basis of Breast Tumor Heterogeneity

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 237 - 257

Published: Jan. 1, 2025

Language: Английский

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High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment

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

Published: March 6, 2024

Introduction Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is a particularly lethal disease that often diagnosed late and refractory to forms treatment. Tumour hypoxia key hallmark PDAC purported contribute multiple facets progression such as treatment resistance, increased invasiveness, metabolic reprogramming, immunosuppression. Methods We used Buffa gene signature score profile transcriptomics datasets from cases. performed cell-type deconvolution expression profiling approaches compare immunological phenotypes cases with low high scores. further supported our findings by qPCR analyses in cell lines cultured hypoxic conditions. Results First, we demonstrated this associated tumour grade reduced survival suggesting correlated progression. Subsequently, compared immune versus (Hypoxia HI vs. Hypoxia LOW ) show levels T cells, NK cells dendritic (DC), including crucial cDC1 subset. Concomitantly, immune-related revealed tumours, mRNA for immunosuppressive molecules were notably elevated Using Random Forest machine learning approach variable selection, identified LGALS3 (Galectin-3) top status confirmed its lines. Discussion In summary, novel associations between mediators PDAC, highlighting avenues improving immunotherapy targeting these combination hypoxia-targeted drugs.

Language: Английский

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