Metabolism-inflammasome crosstalk shapes innate and adaptive immunity DOI Creative Commons
Jun Wu, Xuan Sun, Peng Jiang

et al.

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(5), P. 884 - 903

Published: May 1, 2024

Inflammasomes are a central component of innate immunity and play vital role in regulating immune response. Activation inflammasomes is also indispensable for adaptive immunity, modulating the development response immunity. Recently, increasing studies have shown that metabolic alterations adaptations strongly influence regulate differentiation function system. In this review, we will take holistic view how bridge (especially T cell) crosstalk with signals during responses. And, special attention be paid to control inflammasome-mediated interactions between disease. Understanding regulatory functions would provide new insights into future research directions area may help identify potential targets inflammasome-associated diseases broaden therapeutic avenues.

Language: Английский

Exploiting innate immunity for cancer immunotherapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

Citations

89
The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors DOI Creative Commons
Kaveh Hadiloo,

Siavash Taremi,

Mahmood Heidari

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 28, 2023

Abstract Today, adoptive cell therapy has many successes in cancer therapy, and this subject is brilliant using chimeric antigen receptor T cells. The CAR with its FDA-approved drugs, could treat several types of hematological malignancies thus be very attractive for treating solid cancer. Unfortunately, the cannot functional cancers due to unique features. This treatment method harmful adverse effects that limit their applications, so novel treatments must use new cells like NK cells, NKT macrophage Among these innate features, are more tumor seem a better candidate prior methods. have vital roles microenvironment and, direct effect, can eliminate efficiently. In addition, being part immune system, attended sites. With high infiltration, modulations effective. review investigates last achievements CAR-macrophage future immunotherapy method.

Language: Английский

Citations

47
Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response DOI Creative Commons
Alexander Coulton, Jun Murai, Danwen Qian

et al.

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

Published: July 6, 2024

Abstract The paradigm for macrophage characterization has evolved from the simple M1/M2 dichotomy to a more complex model that encompasses broad spectrum of phenotypic diversity, due differences in ontogeny and/or local stimuli. We currently lack an in-depth pan-cancer single cell RNA-seq (scRNAseq) atlas tumour-associated macrophages (TAMs) fully captures this complexity. In addition, increased understanding diversity could help explain variable responses cancer patients immunotherapy. Our includes well established subsets as number additional ones. associate composition with tumour phenotype and show can vary between primary metastatic tumours growing sites like liver. also examine macrophage-T functional cross talk identify two TAMs associated T activation. Analysis TAM signatures large cohort immune checkpoint inhibitor-treated (CPI1000 + ) multiple response, including presence subset upregulate collagen-related genes. Finally, we demonstrate utility our data resource reference mapping novel datasets using projection. Overall, these advances represent important step both classification overcoming resistance immunotherapies cancer.

Language: Английский

Citations

28
Serine synthesis sustains macrophage IL-1β production via NAD+-dependent protein acetylation DOI Creative Commons
Chuanlong Wang, Qingyi Chen, Siyuan Chen

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 744 - 759.e6

Published: Jan. 23, 2024

Language: Английский

Citations

21
From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy DOI Creative Commons
Eleonora Pinto, Lisa A. Lione, Mirco Compagnone

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 4, 2025

Abstract In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to approval of six therapeutic products for haematological malignancies. Recently, potential this also been demonstrated in non-tumoral diseases. Currently, manufacturing process produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive. It involves multiple steps, including collection T from patients or healthy donors, vitro engineering expansion, finally reinfusion into patients. Therefore, despite impressive clinical outcomes, ex vivo makes out reach many cancer Direct could be a more rapid solution able circumvent both complexity costs associated with manufactured cells. This novel approach allows completely eliminate manipulation expansion while producing populations directly vivo. To date, several studies have feasibility reprogramming, by employing injectable viral- nanocarrier-based delivery platforms tumour animal models. Additionally, production might reduce incidence, at least severity, systemic toxicities frequently occurring produced cells, such as cytokine release syndrome immune effector cell-associated neurotoxicity syndrome. review, we highlight challenges current protocols review latest progresses emerging field therapy, comparing various so far investigated. Moreover, offer an overview advantages deriving reprogramming other types, Natural Killer macrophages, CAR constructs.

Language: Английский

Citations

2
M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors DOI Creative Commons
Yi Huo, Han Zhang,

Longqi Sa

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 28, 2023

Abstract Background Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and functions. CAR-M has shown unique impressive antitumor effects in for solid tumors. However, the polarization state of macrophages can affect effect CAR-M. We hypothesized activity CAR-Ms may be further improved after inducing M1-type polarization. Methods In this report, we constructed HER2-targeting CAR-M, which was composed humanized anti-HER2 scFv, CD28 hinge region FcγRI transmembrane domain intracellular domain. Phagocytosis, tumor-killing capacities, cytokine release were detected with or without M1-polarization pretreatment. Several syngeneic tumor models used to monitor vivo M1-polarized CAR-Ms. Results After LPS combined interferon-γ vitro, found phagocytic capacities against target cells significantly enhanced. The expression costimulatory molecules proinflammatory cytokines also increased By establishing several vivo, demonstrated infusing polarized could effectively suppress progression prolong survival tumor-bearing mice enhanced cytotoxicity. Conclusions our eliminate HER2-positive both vitro M1 ability resulting stronger therapeutic immunotherapy.

Language: Английский

Citations

39
Excitatory amino acid transporter supports inflammatory macrophage responses DOI Creative Commons
Zhending Gan, Yan Guo, Muyang Zhao

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Excitatory amino acid transporters (EAATs) are responsible for excitatory transportation and associated with auto-immune diseases in the central nervous system peripheral tissues. However, subcellular location function of EAAT2 macrophages still obscure. In this study, we demonstrated that LPS stimulation increases expression (coded by Slc1a2) via NF-κB signaling. is necessary inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal mediates glutamate aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis mTORC1. We also found mice myeloid depletion Slc1a2 show alleviated responses LPS-induced systemic inflammation high-fat diet induced obesity. Notably, patients type II diabetes (T2D) have a higher level activation blood macrophages. Taken together, our study links fate decision immune cells, provides potential therapeutic targets treatment diseases.

Language: Английский

Citations

16
Nano‐bio interactions between 2D nanomaterials and mononuclear phagocyte system cells DOI Creative Commons
Jing Zhao, Zheng Chen,

Shanbiao Liu

et al.

BMEMat, Journal Year: 2024, Volume and Issue: 2(2)

Published: Jan. 10, 2024

Abstract Two‐dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly the realms of immunotherapy tissue engineering tumor therapy. These applications necessitate a thorough assessment potential influence 2D nanomaterials on immune cells. Notably, mononuclear phagocyte system (MPS) cells, which play pivotal roles both innate adaptive immunity, are essential maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to prevention foreign body invasion elimination dead or senescent Furthermore, including macrophages dendritic serve as vital bridges between responses. Therefore, understanding nano‐bio interactions is imperative. cellular uptake, cytocompatibility, immunological impact invaluable purposeful design nanomaterials. Herein, we provide an overview latest advancements discuss current challenges future prospects employing field nanomedicine.

Language: Английский

Citations

13
The next frontier in immunotherapy: potential and challenges of CAR-macrophages DOI Creative Commons
Jing Li,

Ping Chen,

Wenxue Ma

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Language: Английский

Citations

13
Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer DOI Creative Commons

Yizhao Chen,

Qianling Xin,

Mengjuan Zhu

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Language: Английский

Citations

2