From cold to hot: mechanisms of hyperthermia in modulating tumor immunology for enhanced immunotherapy DOI Creative Commons

M. Marc Abreu,

Alberto F. Chocron,

David M. Smadja

et al.

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

Published: Feb. 28, 2025

The emergence of immunotherapies has revolutionized cancer treatment by leveraging the immune system to target malignancies, offering new hope where traditional therapies often fall short. Within this context, hyperthermia (HT) re-emerged as a promising adjunctive treatment, capable enhancing effectiveness radiotherapy, chemotherapy, and immunotherapy. HT influences both innate adaptive systems, activity cells such neutrophils, NK cells, dendritic while also modulating tumor microenvironment (TME) promote immunogenic cell death (ICD) reduce immunosuppressive conditions. These effects contribute transformation immunologically “cold” tumors into “hot” tumors, making them more susceptible immune-mediated destruction. Furthermore, can amplify efficacy checkpoint inhibitors (ICIs) improving infiltration, inducing damage-associated molecular pattern (DAMP) release, antigen presentation. Preclinical clinical studies support combination with ICIs, demonstrating improved outcomes in otherwise resistant tumors. However, full therapeutic potential different technologies allowing apply remains be fully understood, further research is needed optimize protocols, explore differential impacts local versus whole-body hyperthermia, identify biomarkers for patient stratification. This review underscores multifaceted role immunity its significantly enhance

Language: Английский

Immunologic tumor microenvironment modulators for turning cold tumors hot DOI Creative Commons
Gholamreza Khosravi, Samaneh Mostafavi,

Sanaz Bastan

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(5), P. 521 - 553

Published: March 29, 2024

Abstract Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within tumor microenvironment (TME). Hot tumors, characterized by heightened activity responsiveness to checkpoint inhibitors (ICIs), stand in stark contrast cold which lack infiltration remain resistant therapy. To overcome evasion mechanisms employed cells, novel immunologic modulators have emerged, particularly ICIs targeting T‐lymphocyte‐associated protein 4 (CTLA‐4) programmed cell death 1/programmed death‐ligand 1(PD‐1/PD‐L1). These agents disrupt inhibitory signals reactivate system, transforming tumors hot ones promoting effective antitumor responses. However, challenges persist, including primary resistance immunotherapy, autoimmune side effects, response heterogeneity. Addressing these requires innovative strategies, deeper mechanistic insights, a combination interventions enhance effectiveness immunotherapies. In landscape cancer medicine, where represent formidable hurdle, understanding TME harnessing its potential reprogram is paramount. This review sheds light current advancements future directions quest for more safer treatment offering hope patients with immune‐resistant tumors.

Language: Английский

Citations

61
Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

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

Citations

44
Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy DOI Creative Commons
Qiang Liu,

Yujing Guan,

Shenglong Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Language: Английский

Citations

17
Design of pH-Responsive Nanomaterials Based on the Tumor Microenvironment DOI Creative Commons

Yunheng Liu,

Lei Si, Yuxuan Jiang

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 705 - 721

Published: Jan. 1, 2025

The metabolic activity of tumor cells leads to the acidification surrounding microenvironment, which provides new strategies for application nanotechnology in cancer therapy.Researchers have developed various types pH-responsive nanomaterials based on acidic microenvironment.This review an in-depth discussion design mechanisms, drug-loading strategies, and pathways microenvironment-responsive nanodrug delivery systems.These materials trigger drug release upon reaching enhancing therapeutic targeting reducing toxicity healthy cells.pH-responsive include organic nanomaterials, inorganic composite nanomaterials.Additionally, this outlines prospects, challenges aiming promote development clinical translation field.

Language: Английский

Citations

3
Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma DOI Open Access
Md. Ataur Rahman,

Meser M. Ali

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 2975 - 2975

Published: Aug. 27, 2024

Malignant gliomas present great difficulties in treatment, with little change over the past 30 years median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing formation new vasculature (antiangiogenic treatments) or destroying formed tumor (vascular disrupting agents) show promise. This study summarizes existing knowledge regarding processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses activation redundant proangiogenic pathways, heightened cell invasion metastasis, induced hypoxia, creation vascular mimicry channels, regulation immune microenvironment. Subsequently, we explore potential strategies overcome this resistance, such as combining other methods, personalizing treatments for each patient, focusing on therapeutic targets, incorporating immunotherapy, utilizing drug delivery systems based nanoparticles. Additionally, would like discuss limitations methods future directions enhance beneficial effects patients GBM. Therefore, review aims research outcome GBM provide a more promising opportunity thoroughly exploring mechanisms investigating novel strategies.

Language: Английский

Citations

10
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment DOI Creative Commons
Jing Wei, Wenke Li, Pengfei Zhang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 26, 2024

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune blockade (ICB) remains critical challenge, characterized by variable response rates and non-durable benefits. However, growing research into complex intrinsic extrinsic characteristics tumors has advanced our understanding mechanisms behind ICI resistance, potentially improving outcomes. Additionally, robust predictive biomarkers are crucial optimizing patient selection maximizing efficacy ICBs. Recent studies emphasized that multiple rational combination strategies can overcome enhance susceptibility ICIs. These findings not only deepen tumor biology but also reveal unique action sensitizing agents, extending benefits in cancer immunotherapy. In this review, we will explore underlying ICIs, discuss significance microenvironment (TIME) biomarkers, analyze current outline alternative effectiveness including personalized

Language: Английский

Citations

10
Functionalized biomimetic nanoparticles loaded with salvianolic acid B for synergistic targeted triple-negative breast cancer treatment DOI Creative Commons
Nuo Cheng, Qianqian Zhou,

Zongfang Jia

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 30, P. 101441 - 101441

Published: Jan. 1, 2025

The therapeutic effect of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) is unsatisfactory. "cold" microenvironment caused by tumor-associated fibroblasts (TAFs) has an adverse on the antitumor response. Therefore, this study, mixed cell membrane-coated porous magnetic nanoparticles (PMNPs) were constructed to deliver salvianolic acid B (SAB) induce response, facilitating transition from a "hot" tumor and ultimately enhancing efficacy inhibitors. PMNP-SAB, which based coating red blood membrane TAF (named PMNP-SAB@RTM), can simultaneously achieve dual effects "immune escape" "homologous targeting". Under influence external field (MF), SAB be targeted concentrated at site. released tumors effectively inhibit production extracellular matrix (ECM) TAFs, promote T-cell infiltration, responses. Ultimately, combination PMNP-SAB@RTM BMS-1 (PD-1/PD-L1 inhibitor 1) inhibited growth. Finally, study presents precise effective new strategy for TNBC immunotherapy basis differentiation microenvironments.

Language: Английский

Citations

1
RNA modifications in cancer DOI Creative Commons

Han Wu,

Shi Chen, Xiang Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

Citations

1
Efficacy of Anti-Cancer Immune Responses Elicited Using Tumor-Targeted IL-2 Cytokine and Its Derivatives in Combined Preclinical Therapies DOI Creative Commons
Sahar Balkhi,

Giorgia Bilato,

Andrea De Lerma Barbaro

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 69 - 69

Published: Jan. 13, 2025

Effective cancer therapies must address the tumor microenvironment (TME), a complex network of cells and stromal components, including endothelial, immune, mesenchymal cells. Durable outcomes require targeting both TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based have shown efficacy in cancers such as metastatic melanoma renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, antibody–drug conjugates, immunocytokines, antibody–cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8+ T lymphocytes natural killer (NK) cells, eliciting potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg activity further improve specificity reduce immunosuppression. Additionally, conjugates peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining immune checkpoint inhibitors (ICIs), agents, radiotherapy has demonstrated synergistic potential. Preclinical clinical studies highlight toxicity enhanced efficacy, overcoming TME-driven suppression. mitigate limitations high-dose soluble therapy, promoting activation adverse This review critically explores advances therapies, focusing on derivatives. Emphasis is placed their role combination strategies, showcasing potential to target effectively. Also, use immunocytokines “in situ” vaccination relieve immunosuppression discussed.

Language: Английский

Citations

1
Fatty acid metabolism influences the immune microenvironment in papillary thyroid cancer and identifies SCD as a novel biomarker DOI Creative Commons
Bingbing Shen, Yu Zhang, Yan Tie

et al.

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

Published: Feb. 27, 2025

Papillary thyroid carcinoma (PTC) is a common endocrine tumor with rapidly increasing incidence. While surgery and radioactive iodine treatment are effective for most patients, they impose significant economic psychological burdens. Metabolic dysregulation, particularly in fatty acid metabolism (FAM), plays critical role cancer progression immune responses. Identifying key FAM-related genes PTC may provide valuable biomarkers potential candidates. We analyzed 309 to build prognostic signature. DEGs were identified multivariate Cox regression model was utilized establish robust signature, which validated by evaluating its associations clinical features, responses, progression. Lastly, we examined the expression of cell lines assessed that silencing SCD disturbs proliferation, invasion, migration cells. three genes, ACACB, ADH1B, SCD, as markers. Immunological analysis uncovered low-risk patients exhibited higher abundance increased checkpoints, indicating better response immunotherapy. In contrast, high-risk showed lower checkpoint expression, suggesting poorer immunotherapy outcomes. Experimental validation demonstrated ACACB ADH1B downregulated, while upregulated lines. Furthermore, inhibited migration, invasion. Our study underscores pivotal regulation PTC. The signature derived from these represents tool predicting outcomes guiding personalized strategies. Among these, stands out promising therapeutic target PTC, warranting further research validate findings uncover underlying molecular mechanisms.

Language: Английский

Citations

1