TP53 Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications DOI Open Access
Chuqi Wang,

Jordan Yong Ming Tan,

N. L. Chitkara

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 3069 - 3069

Published: Sept. 3, 2024

Mutation in p53 is the most frequent event cancer development and a leading cause of therapy resistance due to evasion apoptosis cascade. Beyond chemotherapies radiation therapies, growing evidence indicates that p53-mutant tumors are resistant broad range immune-based such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T, hematopoietic stem cell transplantation (HSCT). This highlights role mutations driving tumor cells. In this review, we first summarize recent studies revealing mechanisms by which evade surveillance from T cells, natural killer (NK) macrophages. We then review how these mutant cells reshape microenvironment (TME), modulating bystander macrophages, neutrophils, regulatory (Treg) foster immunosuppression. Additionally, clinical observations indicative associated with loss or mutations. Finally, discuss therapeutic strategies enhance response wild-type (WT) tumors.

Language: Английский

Macrophages at the interface of the co-evolving cancer ecosystem DOI Creative Commons
Daan J. Kloosterman, Leila Akkari

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1627 - 1651

Published: March 15, 2023

Language: Английский

Citations

200
Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance DOI Creative Commons
Shujing Wang, Jingrui Wang, Zhiqiang Chen

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 10, 2024

Abstract Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and immunosuppressive nature microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components TME. M2-like TAMs are in facilitating metastasis as well augmenting tumors. This review encapsulates mechanisms that use to promote resistance. We also describe emerging therapeutic strategies currently targeting combination with other antitumor drugs, some still undergoing clinical trial evaluation. Furthermore, we summarize analyze various existing approaches for developing novel drugs target overcome resistance, highlighting how can effectively stop growth, metastasis,

Language: Английский

Citations

172
Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers DOI Creative Commons

Liping Pei,

Yang Liu, Lin Liu

et al.

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

Published: Feb. 10, 2023

Abstract In recent years, breakthroughs have been made in tumor immunotherapy. However, immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective only a small percentage of patients solid cancer. How to improve the efficiency cancer immunotherapy an urgent problem be solved. As we all know, state microenvironment (TME) essential factor affecting effectiveness and cancer-associated fibroblasts (CAFs) TME attracted much attention years. one main components TME, CAFs interact with cells by secreting cytokines vesicles, participating ECM remodeling, finally response process. With in-depth study heterogeneity, new strategies are provided for finding targets combination predicting efficacy. this review, focus on role microenvironment, then further elaborate potential mechanisms pathways influencing addition, summarize clinical application value CAFs-related markers cancers.

Language: Английский

Citations

126
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

103
An acid-responsive MOF nanomedicine for augmented anti-tumor immunotherapy via a metal ion interference-mediated pyroptotic pathway DOI

Zhenzhen Feng,

Gui Chen,

Min Zhong

et al.

Biomaterials, Journal Year: 2023, Volume and Issue: 302, P. 122333 - 122333

Published: Sept. 16, 2023

Language: Английский

Citations

83
Carrier-Free Immunotherapeutic Nano-Booster with Dual Synergistic Effects Based on Glutaminase Inhibition Combined with Photodynamic Therapy DOI

Ziyi Mai,

Jing Zhong, Jiasi Zhang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(2), P. 1583 - 1596

Published: Jan. 3, 2023

The immunotherapeutic effect elicited by photodynamic therapy (PDT) is attenuated tumor defense mechanisms associated with glutamine metabolism, including the metabolic regulation of redox homeostasis and limitation immunosuppressive microenvironment (ITM). Herein, a carrier-free nanobooster C9SN dual synergistic effects was constructed self-assembly glutaminase (GLS) inhibitor compound 968 (C968) photosensitizer Chlorin e6. C968-mediated GSH deprivation through inhibiting metabolism prevented PDT-generated reactive oxygen species from being annihilated GSH, amplifying intracellular oxidative stress, which caused severe cell death also enhanced immunogenic (ICD) effect. In addition, genome-wide analysis carried out using RNA-sequencing to evaluate changes in transcriptome induced stress. Thereafter, neoantigens generated ICD promoted maturation dendritic cells, thereby recruiting activating cytotoxic T lymphocytes (CTLs). Meanwhile, remodeled ITM blocking polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, further recruited activated CTLs. Ultimately, this suppressed primary distant tumors. This "kill two birds one stone" strategy would shed light on enhancing immunogenicity alleviating immunosuppression improve PDT.

Language: Английский

Citations

75
Extracellular Vesicles‐Derived Hybrid Nanoplatforms for Amplified CD47 Blockade‐Based Cancer Immunotherapy DOI
Lu Tang, Yue Yin,

Yuqi Cao

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(35)

Published: June 29, 2023

Immunomodulation of tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like phenotype is a promising but challenging strategy. Cleverly, tumor cells overexpress CD47, "don't eat me" signal that ligates with the regulatory protein alpha (SIRPα) on to escape phagocytosis. Thus, effective re-education TAMs "eat type and blocking CD47-SIRPα signaling play pivotal roles in immunotherapy. Herein, it reported hybrid nanovesicles (hEL-RS17) derived from extracellular vesicles M1 decorated RS17 peptide, an antitumor peptide specifically binds CD47 blocks signaling, can actively target remodel TAM phenotypes. Consequently, more infiltrate tissue phagocytize due blockade. By further co-encapsulating chemotherapeutic agent shikonin, photosensitizer IR820, immunomodulator polymetformin hEL-RS17, enhanced effect obtained combinational treatment modality close synergy among each component. Upon laser irradiation, designed SPI@hEL-RS17 nanoparticles exert potent efficacy against both 4T1 breast B16F10 melanoma models, which not only suppresses primary growth also inhibits lung metastasis prevents recurrence, exhibiting great potential boosting blockade-based

Language: Английский

Citations

65
The role of tumor-associated macrophages in tumor immune evasion DOI Creative Commons

Ruizhe Huang,

Ting Kang, Siyu Chen

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

Citations

53
Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy DOI
Sheng Lü, Yifan Li, Yingjie Yu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Language: Английский

Citations

52
Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application DOI Creative Commons
Qian Yang, Shisheng Li,

Haibo Ou

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 28, 2024

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although current tumor treatment methods have therapeutic effect to certain extent, they still some shortcomings such as poor water solubility, short half-life, local systemic toxicity. Therefore, how deliver agent so realize safe effective anti-tumor therapy become urgently be solved in this field. As medium of information exchange material transport between cells, exosomes are considered promising drug delivery carrier due their nano-size, good biocompatibility, natural targeting, easy modification. In review, we summarize recent advances isolation, identification, loading, modification carriers for alongside application therapy. Basic knowledge exosomes, biogenesis, sources, characterization methods, also introduced herein. addition, challenges related use vehicles discussed, along with future trends. This review provides scientific basis exosome systems oncological

Language: Английский

Citations

51