Intimate communications within the tumor microenvironment: stromal factors function as an orchestra DOI Creative Commons
Bing Cheng, Qiang Yu, Wenyu Wang

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Jan. 4, 2023

Extensive studies of the tumor microenvironment (TME) in last decade have reformed view cancer as a cell-centric disease. The microenvironment, especially termed "seed and soil" theory, has emerged key determinant development therapeutic resistance. TME mainly consists cells, stromal cells such fibroblasts, immune other noncellular components. Within TME, intimate communications among these components largely determine fate tumor. pivotal roles stroma, cancer-associated fibroblasts (CAFs), most common component within been revealed tumorigenesis, progression, response, immunity. A better understanding function sheds light on therapy. In this review, we summarize emerging factors, CAFs, drug resistance, immunity with an emphasis their functions epigenetic regulation. Moreover, importance regulation reshaping basic biological principles underpinning synergy between therapy immunotherapy will be further discussed.

Language: Английский

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential DOI Creative Commons
Choong‐Hyun Koh, Suyoung Lee,

Minkyeong Kwak

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(11), P. 2287 - 2299

Published: Nov. 1, 2023

Abstract CD8 T cells play crucial roles in immune surveillance and defense against infections cancer. After encountering antigenic stimulation, naïve differentiate acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic cells, characterized by their ability produce cytokines release granules directly kill target have been recognized as the constituents of predominant T-cell subset. However, emerging evidence suggests distinct subsets that each exhibit unique functions therapeutic potential. This review highlights recent advancements our understanding contributions these various disease pathologies. Understanding diverse is discern complex dynamics responses different settings. Furthermore, development immunotherapeutic approaches specifically regulate function holds great promise for precision medicine.

Language: Английский

Citations

107
Reactive oxygen species-powered cancer immunotherapy: Current status and challenges DOI

Mengying He,

Mengyuan Wang,

Tao Xu

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 356, P. 623 - 648

Published: March 21, 2023

Language: Английский

Citations

89
Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response DOI
Mingle Li, Jungryun Kim, Hyeonji Rha

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6007 - 6023

Published: March 7, 2023

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by release pro-inflammatory cytokines. Our knowledge pyroptosis has expanded beyond cellular level and now includes extracellular responses. In recent years, attracted considerable attention due its potential induce host immunity. For instance, at 2022 International Medicinal Chemistry Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled activation ("PhotoPyro"), emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share Perspective our views on area expound how why "PhotoPyro" could trigger antitumor (i.e., turning so-called "cold" tumors "hot"). doing so, have tried highlight cutting-edge breakthroughs PhotoPyro while suggesting areas future contributions. By providing insights into current state art serving as a resource individuals interested working area, it is hoped that will set stage evolve broadly applicable cancer treatment strategy.

Language: Английский

Citations

87
Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides DOI
Di Huang, Xiao‐Feng Zhu, Shuying Ye

et al.

Nature, Journal Year: 2023, Volume and Issue: 625(7995), P. 593 - 602

Published: Dec. 13, 2023

Language: Английский

Citations

84
Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression DOI Creative Commons
Jinfeng Liu,

Jiaxin Xiang,

Cuiyuan Jin

et al.

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

Published: March 6, 2023

Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but effector components enclosed in vesicles mechanisms involved are largely unknown. The plant Artemisia annua is known an anti-malaria agent that also exhibits wide range of biological activities including immunoregulatory anti-tumor properties with to be further addressed. Here, we isolated purified exosome-like particles from A. annua, which were characterized by nano-scaled membrane-bound shape hence termed artemisia-derived (ADNVs). Remarkably, demonstrated inhibit tumor growth boost immunity mouse model lung cancer, primarily through remolding microenvironment reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via vesicles, molecule induce cGAS-STING pathway driving shift pro-tumor phenotype. Furthermore, our data showed administration ADNVs greatly improved efficacy PD-L1 inhibitor, prototypic immune checkpoint tumor-bearing mice. Together, present study, first time, knowledge, unravels wherein medical mtDNA, nanovesicles, induces immunostimulatory signaling mammalian cells resetting promoting eradication.

Language: Английский

Citations

50
Synergistic efficacy of simultaneous anti-TGF-β/VEGF bispecific antibody and PD-1 blockade in cancer therapy DOI Creative Commons

Mengke Niu,

Ming Yi, Yuze Wu

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 12, 2023

Recently, therapeutic antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) have exerted potent anticancer effect in a variety of tumors. However, blocking the PD-1/PD-L1 axis alone is not sufficient to restore normal immune response. Other negative regulators antitumor immunity, like TGF-β VEGFA, are also involved escape tumor cells induce immunotherapy resistance.We developed novel anti-TGF-β/VEGF bispecific antibody Y332D based on Nano-YBODY™ technology platform. The CCK-8, flow cytometry, SBE4 luciferase reporter assay, western blotting transwell assays were used measure biological activities anti-TGF-β moiety. NFAT luminescent viability assay tube formation anti-VEGF vivo efficacy or combination with PD-1 blockade was evaluated H22, EMT-6, 4T1, AKT/Ras-driven murine hepatocellular carcinoma models. Immunofluorescent staining, RNA-seq quantitative RT-PCR adopted analyze alterations microenvironment.Y332D could maintain specific binding affinities for VEGFA. almost entirely counteracted vitro functions including immunosuppression, activated signaling, epithelial-mesenchymal transition (EMT), VEGF/VEGFR HUVEC proliferation formation. experiment data demonstrated that more effective inhibiting growth metastasis than monotherapies. In therapies, plus exhibited most durable effect. Mechanistically, upregulated density function tumor-infiltrating lymphocytes reinvigorated immunity.Y332D simultaneously block VEGF signalings. comparison monotherapies, combined exerts superior through improving microenvironment.

Language: Английский

Citations

47
Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor DOI
Tiantian Liu, Zehang Zhou, Mengxing Zhang

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 362, P. 502 - 512

Published: Sept. 9, 2023

Language: Английский

Citations

47
Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial DOI Creative Commons
Jun Yin, Jingnan Yuan, Yunjin Li

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2068 - 2078

Published: July 24, 2023

Abstract Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results a phase 1b trial PD-L1 blockade with adebrelimab resectable ESCC. Patients received two doses followed by surgery. The primary endpoints were safety and feasibility; secondary included pathologic complete response (pCR) OS. Our data showed feasibility had been met. Common treatment-related adverse events anorexia (32%) fatigue (16%), without grade 3 or more events. Of 30 patients enrolled trial, 25 underwent successful resection surgery delay 24% major responses including pCR rate 8%. 2-year OS was 92%. Responsive an immune-enriched tumor microenvironment phenotype, whereas nonresponsive greater infiltration cancer-associated fibroblasts at baseline. Clonotypic dynamics pre-existing intratumoral T cells hallmark responsive patients. These findings provide rational for anti-PD-L1 monotherapy as therapeutic strategy ClinicalTrials.gov identifier: NCT04215471 .

Language: Английский

Citations

44
Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

Citations

39
Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer DOI Creative Commons
Takahiko Murayama, Jun Nakayama, Xinpei Jiang

et al.

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(3), P. 468 - 491

Published: Jan. 4, 2024

Abstract Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as “viral mimicry,” has emerged an effective strategy to convert immunologically “cold” tumors into “hot.” Through curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) potent repressor double-stranded (dsRNA) small cell lung cancers (SCLC). Depletion DHX9 induced accumulation dsRNA and triggered tumor-intrinsic immunity. Intriguingly, ablating also aberrant R-loops, which resulted increase DNA damage–derived replication stress SCLCs. In vivo, deletion promoted decrease tumor growth while inducing more immunogenic microenvironment, invigorating responsiveness immune-checkpoint blockade. These findings suggest that is crucial stress, representing promising target for SCLC other genomic instability contributes pathology. Significance: One trigger immune response within enhance immunotherapy efficacy by endogenous “virus-mimetic” accumulation. Here, identify viral-mimicry-inducing factor involved the suppression RNAs R-loops propose novel antitumor See related commentary Chiappinelli, p. 389. This article featured Selected Articles from Issue, 384

Language: Английский

Citations

31