Tumor immunotherapy resistance: Revealing the mechanism of PD-1 / PD-L1-mediated tumor immune escape DOI Creative Commons
Jiawen Cui, Yao Li, Yang Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116203 - 116203

Published: Jan. 26, 2024

Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which significant in regulation of immune evasion by tumors. Nevertheless, considerable number patients develop resistance to anti-PD-1/PD-L1 rendering it ineffective long run. This research focuses on exploring factors PD-1/PD-L1-mediated immunotherapy. Initially, characterized its role facilitating evasion, emphasizing autoimmune homeostasis. Next, primary mechanisms PD-1/PD-L1-based immunotherapy are analyzed, including antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations expression PD-L1 within cells. The possible ramifications altered metabolism, microbiota, DNA methylation also described. Finally, resolution strategies for dealing with discussed, placing particular emphasis personalized therapeutic approaches exploration more potent regimens.

Language: Английский

Nanocomplex‐Mediated In Vivo Programming to Chimeric Antigen Receptor‐M1 Macrophages for Cancer Therapy DOI
Mikyung Kang, Seong Ho Lee,

Miji Kwon

et al.

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(43)

Published: Sept. 12, 2021

Abstract Chimeric antigen receptor‐T (CAR‐T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to complex ex vivo cell‐manufacturing procedures and low therapeutic efficacy against solid tumors. The limited effects partially CAR‐T infiltration tumors inactivation of cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented in program macrophages, which can intrinsically penetrate tumors, into CAR‐M1 macrophages displaying enhanced cancer‐directed phagocytosis anti‐tumor activity. In injected nanocomplexes macrophage‐targeting nanocarriers CAR‐interferon‐γ‐encoding plasmid DNA induce that capable CAR‐mediated cancer phagocytosis, immunomodulation, inhibition growth. Together, this study describes an off‐the‐shelf CAR‐macrophage therapy effective avoids costly processes CAR‐cell manufacturing.

Language: Английский

Citations

128
Engineered Bacterial Outer Membrane Vesicles as Controllable Two‐Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy DOI
Qingqing Feng, Xiaotu Ma, Keman Cheng

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(40)

Published: Aug. 20, 2022

The most immune cells infiltrating tumor microenvironment (TME), tumor-associated macrophages (TAMs) closely resemble immunosuppressive M2-polarized macrophages. Moreover, exhibit high expression of CD47 "don't eat me" signal, which obstructs macrophage phagocytosis. precise and efficient activation TAMs is a promising approach to immunotherapy; however, re-education remains challenge. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate Here, an OMV-based controllable two-way adaptor reported, in nanobody (CD47nb) fused onto OMV surface (OMV-CD47nb), with the coated polyethylene glycol (PEG) layer containing diselenide bonds (PEG/Se) form PEG/Se@OMV-CD47nb. PEG/Se modification not only mitigates immunogenicity OMV-CD47nb, thereby remarkedly increasing dose be administered safely through intravenous injection, but also equips formulation radiation-triggered controlled release OMV-CD47nb. Application radiation tumors mice injected nanoformulation results remodeling TME. As adaptors, OMV-CD47nb activates TAM phagocytosis via multiple pathways, including induction M1 polarization blockade signal. this stimulation T cell-mediated antitumor immunity effective antigen presentation.

Language: Английский

Citations

123
Harnessing anti‐tumor and tumor‐tropism functions of macrophages via nanotechnology for tumor immunotherapy DOI Creative Commons

Yanhui Zheng,

Yaobao Han,

Qiao Sun

et al.

Exploration, Journal Year: 2022, Volume and Issue: 2(3)

Published: Feb. 25, 2022

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in immunotherapy. As a class of professional phagocytes and antigen-presenting cells innate immune system, can not only directly engulf clear cells, but also play roles presenting tumor-specific antigen to initiate adaptive immunity. However, tumor-associated (TAMs) usually display tumor-supportive M2 phenotype rather than anti-tumor M1 phenotype. They support escape immunological surveillance, aggravate progression, impede T cell Although many TAMs-modulating agents have shown success therapy multiple tumors, they face enormous challenges including poor accumulation off-target side effects. An alternative solution is use advanced nanostructures, which deliver augment therapeutic efficacy, serve as modulators TAMs. Another important strategy exploitation macrophage-derived components tumor-targeting delivery vehicles. Herein, we summarize recent advances targeting engineering for immunotherapy, (1) direct indirect effects on augmentation immunotherapy (2) strategies macrophage-based drug carriers. The existing perspectives immunotherapies are highlighted.

Language: Английский

Citations

118
Tumor Associated Macrophages: Origin, Recruitment, Phenotypic Diversity, and Targeting DOI Creative Commons
Tetiana Hourani, James A. Holden, Wenyi Li

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Dec. 20, 2021

The tumor microenvironment (TME) is known to have a strong influence on tumorigenesis, with various components being involved in suppression and growth. A protumorigenic TME characterized by an increased infiltration of associated macrophages (TAMs), where their presence strongly progression, therapy resistance, poor survival rates. This association between the TAMs therapeutic outcomes are stemming increasing interest investigating as potential target cancer treatment. Prominent mechanisms targeting include: blocking recruitment, stimulating repolarization, depletion methods. For enhancing specificity multiple nanomaterials currently explored for precise delivery chemotherapeutic cargo, including conjugation TAM-targeting peptides. In this paper, we provide focused literature review macrophage biology relation role tumorigenesis. First, discuss origin, recruitment mechanisms, phenotypic diversity based recent investigations literature. Then paper provides detailed current methods TAMs, use novel therapeutics.

Language: Английский

Citations

114
Advances in PET imaging of cancer DOI
Johannes Schwenck, Dominik Sonanini, Jonathan Cotton

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(7), P. 474 - 490

Published: May 31, 2023

Language: Английский

Citations

108
Tumor-associated macrophages: an effective player of the tumor microenvironment DOI Creative Commons
Udit Basak, Tania Sarkar, Sumon Mukherjee

et al.

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

Published: Nov. 16, 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up majority invading immune components, which are further categorized as anti-tumor M1 pro-tumor M2 subtypes. While known to have anti-cancer properties, recognized extend a protective role tumor. As result, manipulates TME in such way that it induces macrophage infiltration switching bias secure its survival. This M2-TAM promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, manipulation an immunosuppressive state. additionally promote emergence stem (CSCs), their ability originate, metastasize, relapse into tumors. CSCs also help revealing escape survival strategies during initiation phases. review describes reasons immunotherapy failure and, thereby, devises better impair tumor-TAM crosstalk. study will shed light on understudied TAM-mediated address much-needed holistic approach therapy, encompasses targeting cells, CSCs, all at same time.

Language: Английский

Citations

94
Current advance of nanotechnology in diagnosis and treatment for malignant tumors DOI Creative Commons

Bilan Wang,

Shiqi Hu, Yan Teng

et al.

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

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

Citations

87
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

84
Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle DOI
Tuying Yong,

Zhaohan Wei,

Lu Gan

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(52)

Published: June 21, 2022

Although immunotherapy harnessing activity of the immune system against tumors has made great progress, treatment efficacy remains limited in most cancers. Current anticancer is primarily based on T-cell-mediated cellular immunity, which highly relies efficiency triggering cancer-immunity cycle, namely, tumor antigen release, presentation by presenting cells, T cell activation, recruitment and infiltration cells into tumors, recognition killing cells. Unfortunately, these immunotherapies are restricted inefficient drug delivery acting only a single step cycle. Due to high biocompatibility, low immunogenicity, intrinsic targeting, easy chemical genetic manipulation, extracellular vesicle (EV)-based systems widely used amplify responses serving as an integrated platform for multiple drugs or therapeutic strategies synergistically activate several steps This review summarizes various mechanisms related affecting cycle disorders. Meanwhile, preparation application EV-based modulating introduced, especially improvement tumors. Finally, opportunities challenges translational clinical applications briefly discussed.

Language: Английский

Citations

82
CSF1R inhibitors are emerging immunotherapeutic drugs for cancer treatment DOI
Jiachen Wen, Siyuan Wang, Rongxian Guo

et al.

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 245, P. 114884 - 114884

Published: Oct. 30, 2022

Language: Английский

Citations

82