The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Год журнала: 2023, Номер 56(10), С. 2188 - 2205

Опубликована: Окт. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Язык: Английский

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Reprogramming tumour-associated macrophages to outcompete cancer cells

Nature, Год журнала: 2023, Номер 619(7970), С. 616 - 623

Опубликована: Июнь 28, 2023

Язык: Английский

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Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Язык: Английский

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A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Язык: Английский

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Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Сен. 3, 2024

Abstract Tumor cells possess complex immune evasion mechanisms to evade system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) modulate cell functions. When a is sufficiently immunogenic, it can activate cytotoxic T-cells target and destroy it. However, tumors adapt by manipulating their pathways, particularly glucose, amino acid, lipid metabolism, create an immunosuppressive TME that promotes escape. These alterations impact function differentiation of non-tumor within TME, such as inhibiting effector T-cell activity while expanding regulatory myeloid-derived suppressor cells. Additionally, these changes lead imbalance in cytokine chemokine secretion, further enhancing landscape. Emerging research increasingly focusing on roles evaluating how reprogrammed metabolism influence functional ultimately aid evasion. Despite our incomplete understanding intricate interactions between cells, connection elements presents significant challenges for cancer immunotherapy. This review highlights altered providing new insights could facilitate development novel immunotherapies.

Язык: Английский

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NAMPT‐Driven M2 Polarization of Tumor‐Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer

Advanced Science, Год журнала: 2024, Номер 11(14)

Опубликована: Фев. 2, 2024

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression cancer cells themselves, but are limited respect to role other within tumor microenvironment (TME) during colorectal (CRC) progression. Using single‐cell RNA sequencing (scRNA‐seq) data, it founded that NAMPT highly expressed SPP1 + tumor‐associated macrophages (TAMs), unique subset TAMs associated immunosuppressive activity. A high gene signature correlated worse prognostic outcomes CRC patients. The effect Nampt deletion myeloid compartment mice development explored. deficiency resulted HIF‐1α destabilization, leading reduction M2‐like TAM polarization. caused significant decreases efferocytosis activity macrophages, which enhanced STING signaling and induction type I IFN‐response genes. Expression these genes contributed anti‐tumoral immunity via potentiation cytotoxic T cell TME. Overall, findings suggest NAMPT‐initiated TAM‐specific can be useful predicting poor patient outcomes; strategies aimed at targeting may provide promising therapeutic approach for building an immunostimulatory TME

Язык: Английский

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Targeting macrophages in cancer immunotherapy: Frontiers and challenges

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and checkpoint blockade. Nevertheless, cells encounters formidable hurdles. Macrophages, serving pivotal link between innate adaptive immunity, play crucial roles phagocytosis, cytokine secretion, antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention. We aim to provide most cutting-edge insights future perspectives for therapies, fostering development novel effective treatments. To date, forefront strategies macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, phagocytosis checkpoints. Macrophages are characterized by remarkable diversity offering unique therapeutic target. In this context, we critically analyze innovative aimed at transforming macrophages from M2 (tumor-promoting) M1 (tumor-suppressing) phenotype. Furthermore, delve into design principles, developmental progress, advantages CAR-macrophages. Additionally, illuminate challenges encountered checkpoints on propose potential overcome these obstacles.

Язык: Английский

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Reprogramming tumor-associated macrophages to outcompete endovascular endothelial progenitor cells and suppress tumor neoangiogenesis

Immunity, Год журнала: 2023, Номер 56(11), С. 2555 - 2569.e5

Опубликована: Ноя. 1, 2023

Язык: Английский

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EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth

Cancer Discovery, Год журнала: 2024, Номер 14(3), С. 524 - 545

Опубликована: Янв. 19, 2024

Abstract The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression fuel novel therapies. Elevated surfactant and GM-CSF secretion from transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation, which supports tumor growth by rewiring inflammatory functions lipid metabolism. TA-AM properties are driven increased GM-CSF–PPARγ signaling inhibition airway or PPARγ TA-AMs suppresses cholesterol efflux cells, impairs EGFR phosphorylation restrains LUAD progression. In absence metabolic support, cells compensate increasing synthesis, blocking simultaneous with statin therapy further progression increases proinflammatory immune responses. These results reveal new therapeutic combinations for immunotherapy-resistant EGFR-mutant LUADs demonstrate how cancer can metabolically co-opt through provide nutrients that promote oncogenic growth. Significance: Alternate strategies harnessing anticancer innate immunity required cancers poor response rates T cell–based immunotherapies. This study identifies a targetable, mutually supportive, relationship between macrophages epithelium, is exploited tumors obtain immunologic support sustain proliferation signaling. article featured Selected Articles Issue, p. 384

Язык: Английский

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Cancer immunometabolism: advent, challenges, and perspective

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Апрель 5, 2024

Abstract For decades, great strides have been made in the field of immunometabolism. A plethora evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism center stage innate and adaptive immunomodulation. Given this, we focus changes immunometabolism, a converging series biochemical events that alters immune cell function, propose roles played by diversified metabolic derivatives enzymes, emphasize key metabolism-related checkpoints distinct types, discuss ongoing upcoming realities treatment. It is expected future research will reduce current limitations immunotherapy provide positive hand responses exert broader therapeutic role.

Язык: Английский

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