Convergent inducers and effectors of T cell paralysis in the tumour microenvironment DOI
Douglas Hanahan, Olivier Michielin, Mikaël J. Pittet

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

Neutrophil phenotypes and functions in cancer: A consensus statement DOI Creative Commons

Daniela F. Quail,

Borko Amulic, Monowar Aziz

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(6)

Published: May 6, 2022

Neutrophils are the first responders to infection and inflammation thus a critical component of innate immune defense. Understanding behavior neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile infectious diseases; however, field cancer is comparatively young. Here, we summarize key concepts current knowledge gaps related diverse roles throughout progression. We discuss sources neutrophil heterogeneity provide recommendations on nomenclature for states that distinct maturation activation. address discrepancies literature highlight need technical standards ought be considered between laboratories. Finally, review emerging questions biology immunity cancer. Overall, emphasize more population than previously appreciated may present novel unexplored opportunities treat

Language: Английский

Citations

218

Neutrophil profiling illuminates anti-tumor antigen-presenting potency DOI Creative Commons
Yingcheng Wu, Jiaqiang Ma, Xupeng Yang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1422 - 1439.e24

Published: March 1, 2024

Language: Английский

Citations

110

Neutrophil diversity in inflammation and cancer DOI Creative Commons
Silvia Carnevale, Irene Di Ceglie, Giovanna Grieco

et al.

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

Published: April 26, 2023

Neutrophils are the most abundant circulating leukocytes in humans and first immune cells recruited at site of inflammation. Classically perceived as short-lived effector with limited plasticity diversity, neutrophils now recognized highly heterogenous cells, which can adapt to various environmental cues. In addition playing a central role host defence, involved pathological contexts such inflammatory diseases cancer. The prevalence these conditions is usually associated detrimental responses poor clinical outcomes. However, beneficial for emerging several contexts, including Here we will review current knowledge neutrophil biology heterogeneity steady state during inflammation, focus on opposing roles different contexts.

Language: Английский

Citations

49

Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives DOI Creative Commons

Ke-Yu Shen,

Ying Zhu,

Sun‐Zhe Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Language: Английский

Citations

49

Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment DOI Open Access
Yunkun Li, Yahui Wu,

Zaixiang Fang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

Citations

48

Roles of exosomes in immunotherapy for solid cancers DOI Creative Commons
C. Lyu, Haifeng Sun, Zhenqiang Sun

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 1, 2024

Abstract Although immunotherapy has made breakthrough progress, its efficacy in solid tumours remains unsatisfactory. Exosomes are the main type of extracellular vesicles that can deliver various intracellular molecules to adjacent or distant cells and organs, mediating biological functions. Studies have found exosomes both activate immune system inhibit system. The antigen major histocompatibility complex (MHC) carried make it possible develop them as anticancer vaccines. derived from blood, urine, saliva cerebrospinal fluid be used ideal biomarkers cancer diagnosis prognosis. In recent years, exosome-based therapy great progress fields drug transportation immunotherapy. Here, we review composition sources microenvironment further elaborate on potential mechanisms pathways by which influence for cancers. Moreover, summarize clinical application prospects engineered exosome vaccines Eventually, these findings may open up avenues determining diagnosis, treatment, prognosis

Language: Английский

Citations

45

Neutrophils in Cancer immunotherapy: friends or foes? DOI Creative Commons
Xueqin Huang, Eugenie Nepovimová, Vojtěch Adam

et al.

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

Published: May 18, 2024

Abstract Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species matrix metalloproteinase 9, within tumor microenvironment. They also modulate expression necrosis factor-related apoptosis-inducing ligand Fas ligand, augmenting their capacity to induce cell apoptosis. Their involvement antitumor regulation synergistically activates network bolstering anticancer effects. Paradoxically, can succumb influence tumors, triggering signaling cascades such as JAK/STAT, which deactivate system network, thereby promoting evasion by malignant cells. Additionally, neutrophil granular constituents, elastase vascular endothelial growth factor, intricately fuel proliferation, metastasis, angiogenesis. Understanding mechanisms that guide collaborate with other cells for comprehensive eradication is crucial enhancing efficacy therapeutics. In this review, we illuminate underlying governing neutrophil-mediated support or inhibition progression, particular focus on elucidating internal external factors polarization. We provide an overview recent advances clinical research regarding therapy. Moreover, future prospects limitations are discussed, aiming fresh insights development innovative treatment strategies targeting neutrophils.

Language: Английский

Citations

45

Engineering and Targeting Neutrophils for Cancer Therapy DOI Creative Commons
Jiahui Zhang, Jianmei Gu, Xu Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 7, 2024

Neutrophils are the most abundant white blood cells in circulation and act as first line of defense against infections. Increasing evidence suggests that neutrophils possess heterogeneous phenotypes functional plasticity human health diseases, including cancer. play multifaceted roles cancer development progression, an N1/N2 paradigm is proposed, where N1 exert anti-tumor properties while N2 display tumor-supportive immune-suppressive functions. Selective activation beneficial neutrophil population targeted inhibition or re-polarization tumor-promoting has shown important potential tumor therapy. In addition, due to natural inflammation-responsive physical barrier-crossing abilities, their derivatives (membranes extracellular vesicles (EVs)) regarded advanced drug delivery carriers for enhanced targeting improved therapeutic efficacy. this review, recent advances engineering remodeling microenvironment (TME) comprehensively presented. This review will provide a broad understanding

Language: Английский

Citations

31

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy DOI
Ninad Kumbhojkar, Supriya Prakash, Tatsuya Fukuta

et al.

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(5), P. 579 - 592

Published: Feb. 29, 2024

Language: Английский

Citations

29

CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors DOI Creative Commons
Ferdinandos Skoulidis, Haniel A. Araújo, Minh Truong

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8038), P. 462 - 471

Published: Oct. 9, 2024

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) CTLA4 inhibitors and PD-1 or PD-L1 (hereafter, PD-(L)1 inhibitors) is associated higher rates of anti-tumour activity immune-related toxicities, when compared treatment alone. However, there are currently no validated biomarkers to identify which will benefit from ICB1,2. Here we show that NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical ICB inhibitor durvalumab tremelimumab, but not alone, added chemotherapy randomized phase III POSEIDON trial3. Unbiased genetic screens identified loss both these as independent drivers resistance inhibition, showed Keap1 was strongest genomic predictor efficacy—a finding confirmed several mouse models Kras-driven NSCLC. In patients, alterations were an adverse microenvironment, characterized by a preponderance suppressive myeloid cells depletion CD8+ cytotoxic T cells, relative sparing CD4+ effector subsets. Dual potently engaged reprogrammed cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that—together cells—contributed efficacy. These data support use chemo-immunotherapy mitigate inhibition alterations. Alterations can likely combinations chemotherapy.

Language: Английский

Citations

26