Exploiting innate immunity for cancer immunotherapy

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

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Inflammation: A New Look at an Old Problem

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4596 - 4596

Published: April 21, 2022

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It defined by a number universal components, including oxidative stress, cellular response DNA damage, unfolded protein mitochondrial and endoplasmic reticulum changes autophagy, inflammasome formation, non-coding RNA response, formation an inducible network signaling pathways, epigenetic changes. The presence receptor secretory phenotype many the cause tissue pro-inflammatory stress. key phenomenon determining occurrence classical inflammatory focus microvascular (exudation, leukocyte migration alteration zone). This same reaction at systemic level leads development life-critical inflammation. From this standpoint, we can characterize common mechanisms pathologies differ their clinical appearance. division inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects also described review. aim review provide theoretical arguments for need up-to-date theory relationship between human pathological processes based on integrative role molecular

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

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

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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Circulating immunotherapy strategy based on pyroptosis and STING pathway: Mn-loaded paclitaxel prodrug nanoplatform against tumor progression and metastasis

Biomaterials, Journal Year: 2024, Volume and Issue: 306, P. 122472 - 122472

Published: Jan. 23, 2024

Language: Английский

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Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

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Malignant Tumors in Vagal-innervated Organs: Exploring Its Homeostatic Role

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217539 - 217539

Published: Feb. 1, 2025

Language: Английский

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Trained immunity: Target for prophylaxis and therapy

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(11), P. 1776 - 1791

Published: Nov. 1, 2023

Language: Английский

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IGF2BP family of RNA-binding proteins regulate innate and adaptive immune responses in cancer cells and tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 12, 2023

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP1, IGF2BP2, and IGF2BP3) are a family of RNA-binding that play an essential role in the development disease by regulating mRNA stability translation critical regulators cell division metabolism. Genetic chemical inhibition these slows down cancer proliferation, decreases invasiveness, prolongs life span variety animal models. The induction tissues' immunogenicity is increasingly recognized, but, impact IGF2BPs on innate adaptive immune responses not fully understood. Here we report downregulation IGF2BP1, 2, 3 expression facilitates interferon beta-stimulated genes. IGF2BP1 has greater effect beta gamma signaling compared to IGF2BP2 IGF2BP3 paralogs. We demonstrate knockdown or knockout significantly potentiates induced IFNβ IFNγ. Mouse melanoma cells with Igf2bp knockouts increased MHC I (H-2) induce intracellular Ifn-γ syngeneic T-lymphocytes vitro. Increased immunogenicity, associated Igf2bp1 inhibition, "inflames" mouse tumors microenvironment SM1/C57BL/6 SW1/C3H models measured two-fold increase NK tumor-associated myeloid cells. Finally, efficiency anti-PD1 immunotherapy model more efficient lack expression. Our retrospective data analysis immunotherapies human patients indicates high levels resistance poor prognosis. In summary, our study provides evidence IGF2BP tumor establishes those RBPs as immunotherapeutic targets cancer.

Language: Английский

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The role of metabolic reprogramming of tumor-associated macrophages in shaping the immunosuppressive tumor microenvironment

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114504 - 114504

Published: March 14, 2023

Macrophages are potent immune effector cells in innate immunity and exert dual-effects the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) make up a significant portion of TME cells. Similar to M1/M2 macrophages, TAMs also highly plastic, their functions regulated by cytokines, chemokines other factors TME. The metabolic changes significantly associated with polarization towards protumour or antitumour phenotype. metabolites generated via TAM reprogramming turn promote progression tolerance. In this review, we explore terms energy, amino acid fatty metabolism potential roles these suppression.

Language: Английский

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Development and validation of a new prognostic immune–inflammatory–nutritional score for predicting outcomes after curative resection for intrahepatic cholangiocarcinoma: A multicenter study

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 31, 2023

Background Immune function, nutrition status, and inflammation influence tumor initiation progression. This was a retrospective multicenter cohort study that investigated the prognostic value clinical relevance of immune-, inflammatory-, nutritional-related biomarkers to develop novel immune–inflammatory–nutritional score (PIIN score) for patients with intrahepatic cholangiocarcinoma (ICC). Methods The data 571 (406 in training set 165 validation set) were collected from four large hepato-pancreatico-biliary centers ICC who underwent surgical resection between January 2011 September 2017. Twelve blood PIIN using LASSO Cox regression model. predictive further assessed datasets. Afterward, nomograms combining other clinicopathological parameters developed validated based on calibration curve, time-dependent AUC curves, decision curve analysis (DCA). primary outcomes evaluated overall survival (OS) recurrence-free (RFS) day ICC. Results Based albumin–bilirubin (ALBI) grade, neutrophil- to- lymphocyte ratio (NLR), nutritional index (PNI), systemic immune- (SII) biomarkers, classified into high-risk low-risk groups could be calculated. Patients scores had shorter OS (training set, p < 0.001; = 0.003) RFS 0.002) than scores. high also associated larger tumors (≥5 cm), lymph node metastasis (N1 stage), multiple tumors, grade or TNM (tumor (T), nodes (N), metastases (M)) stage. Furthermore, significant independent factor both (p 0.001) cohorts, respectively. A PIIN-nomogram individualized prediction constructed by integrating variables yielded better performance Conclusion score, immune–inflammatory–nutritional-related biomarker, predicts prognosis resected can reliable tool after surgery. Our findings provide insights role cancer-related immune disorders, inflammation, malnutrition.

Language: Английский

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