Stromal cells in the tumor microenvironment: accomplices of tumor progression?

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 4, 2023

Abstract The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), cellular components include cancer non-malignant such as immune stromal cells. These three types establish complex signals in the body further influence genesis, development, metastasis participate resistance to anti-tumor therapy. It has attracted scholars study TME due significant efficacy checkpoint inhibitors (ICI) chimeric antigen receptor T (CAR-T) solid tumors hematologic tumors. After more than 10 years efforts, role strategy treating based on have developed rapidly. Moreover, ICI been recommended by guidelines first- or second-line treatment strategies a variety At same time, another major class TME, which also play very important metabolism, growth, metastasis, evasion resistance. Stromal can be recruited from neighboring non-cancerous host formed transdifferentiation they development drug secreting various factors exosomes, participating angiogenesis regulating response matrix. However, with deepening understanding cells, people found that not only effect promoting but inhibit some cases. In this review, we will introduce origin well specific mechanism tumorigenesis for We focus tumor-associated fibroblasts (CAFs), mesenchymal stem (MSCs), adipocytes (CAAs), endothelial (TECs) pericytes (PCs)

Language: Английский

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TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells

Redox Biology, Journal Year: 2022, Volume and Issue: 56, P. 102451 - 102451

Published: Aug. 28, 2022

Language: Английский

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The theory of tumor ecosystem

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(7), P. 587 - 608

Published: June 1, 2022

Abstract Cancer cells can be conceived as “living organisms” interacting with cellular or non‐cellular components in the host internal environment, not only local tumor microenvironment but also distant organ niches, well immune, nervous and endocrine systems, to construct a self‐sustainable ecosystem. With increasing evidence for systemic tumor‐host interplay, we predict that new era of cancer therapy targeting ecosystemic vulnerability human malignancies has come. Revolving around ecosystem scoped different hierarchies primary, regional, distal onco‐spheres, comprehensively review interaction among their microenvironment, highlighting material energy flow ecological homeostasis an driving force. We substantiate knowledge visualizing, modelling subtyping this dynamically intertwined network recent technological advances, discuss ecologically rational strategies more effective therapies.

Language: Английский

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Pericytes in the tumor microenvironment

Cancer Letters, Journal Year: 2023, Volume and Issue: 556, P. 216074 - 216074

Published: Jan. 20, 2023

Pericytes are a type of mural cell located between the endothelial cells capillaries and basement membrane, which function to regulate capillary vasomotor maintain normal microcirculation local tissues organs have been identified as significant component in tumor microenvironment (TME). various interactions with different components TME, such constituting pre-metastatic niche, promoting growth cancer drug resistance through paracrine activity, inducing M2 macrophage polarization. While changes TME can affect number, phenotype, molecular markers pericytes. For example, pericyte detachment from facilitates situ invade circulating blood is beneficial membrane enzymatic hydrolysis proliferation budding, contribute angiogenesis metastasis. In this review, we discuss emerging role pericytes treatment related This review aimed provide more comprehensive understanding relationship tumors ideas for prevention malignant tumors.

Language: Английский

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Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(4), P. 693 - 710.e8

Published: March 23, 2023

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying regulators, we examine microenvironment in glioma and find that tumor-infiltrating T cells mainly confined perivascular cuffs express high levels of CCR5, CXCR3, programmed cell death protein 1 (PD-1). Combined analysis clustering with receptor (TCR) clone expansion shows potential tumor-killing categorized into pre-exhausted/exhausted effector CD8+ subsets, as well cytotoxic CD4+ subsets. Notably, a distinct subpopulation exhibits innate-like features preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, demonstrate IL-8-producing T, myeloid, tumor orchestrate myeloid-derived suppressor infiltration angiogenesis, which results enhanced growth but reduced ICB efficacy. Antibody-mediated IL-8 or inhibition its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight combinational immunotherapy target for glioma.

Language: Английский

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Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Language: Английский

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Targeting cytokine and chemokine signaling pathways for cancer therapy

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

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Novel strategies for cancer immunotherapy: counter-immunoediting therapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: April 13, 2023

Abstract The advent of immunotherapy has made an indelible mark on the field cancer therapy, especially application immune checkpoint inhibitors in clinical practice. Although proven its efficacy and safety some tumors, many patients still have innate or acquired resistance to immunotherapy. emergence this phenomenon is closely related highly heterogeneous microenvironment formed by tumor cells after undergoing immunoediting. process immunoediting refers cooperative interaction between system that involves three phases: elimination, equilibrium, escape. During these phases, conflicting interactions result formation a complex microenvironment, which contributes acquisition different levels cells. In review, we summarize characteristics phases corresponding therapeutic tools, propose normalized strategies based immunophenotyping. retrograded through targeted interventions immunoediting, making context precision therapy most promising cure cancer.

Language: Английский

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The role of endothelial cell–pericyte interactions in vascularization and diseases

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Endothelial cells (ECs) and pericytes (PCs) are crucial components of the vascular system, with ECs lining inner layer blood vessels PCs surrounding capillaries to regulate flow angiogenesis. Intercellular communication between is vital for formation, stability, function vessels. Various signaling pathways, such as endothelial growth factor/vascular factor receptor pathway platelet-derived factor-B/platelet-derived receptor-β pathway, play roles in PCs. Dysfunctional these associated various diseases, including central nervous system disorders, certain types cancers. review: This review aimed explore diverse formation reshaping focused on essential pathways that facilitate investigated how disruptions may contribute disease. Additionally, explored potential therapeutic targets, future research directions, innovative approaches, investigating impact EC-PCs novel systemic addressing resistance antiangiogenic drugs, developing medications enhance efficacy. Key scientific concepts Disordered EC-PC intercellular plays a role abnormal vessel thus contributing progression diseases development drugs. Therefore, studies interactions have high clinical relevance.

Language: Английский

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Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Feb. 22, 2022

Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth resistance to alkylating chemotherapy. Autophagy induction one of hallmark effects anti-GB therapies with temozolomide (TMZ). However, non-classical form autophagy, autophagy-based unconventional secretion, also called secretory autophagy its role in regulating sensitivity GB TMZ remains unclear. There an urgent need illuminate mechanism develop novel therapeutic targets for GB.Cancer genome databases paired-GB patient samples or without treatment were used assess relationship between HMGB1 mRNA levels overall survival. The protein level was measured immunohistochemistry, ELISA, Western blot qRT-PCR. cells engineered express a chimeric autophagic flux reporter consisting mCherry, GFP LC3B. microenvironment (TME) analyzed intracranial implantation GL261 cells. Coimmunoprecipitation (Co-IP) blotting performed test RAGE-NFκB-NLRP3 inflammasome pathway.The exocytosis induced dependent on autophagy. contributed M1-like polarization associated macrophages (TAMs) enhanced TMZ. Mechanistically, RAGE acted as receptor TAMs through pathway, TAMs. Clinically, elevated sera may serve beneficial therapeutic-predictor patients under treatment.We demonstrated that facilitates enhance acts key regulator crosstalk tumor-suppressive be considered adjuvant chemotherapeutic agent

Language: Английский

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