Cancer cells impair monocyte-mediated T cell stimulation to evade immunity DOI Creative Commons

Anais Elewaut,

Guillem Estivill, Felix Bayerl

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Abstract The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses 1,2 . Within the microenvironment, CD8 + T undergo full effector differentiation acquire cytotoxic functions in specialized niches 3–7 Although interactions with type 1 conventional dendritic have been implicated this process 3–5,8–10 , underlying cellular players molecular mechanisms remain incompletely understood. Here we show that inflammatory monocytes can adopt a pivotal role intratumoral cell stimulation. These express Cxcl9 Cxcl10 Il15 but contrast to cells, which cross-present antigens, obtain present peptide–major histocompatibility complex class I complexes from through ‘cross-dressing’. Hyperactivation of MAPK signalling hampers coordinately blunting production interferon (IFN-I) cytokines inducing secretion prostaglandin E 2 (PGE ), impairs monocyte state Enhancing IFN-I cytokine blocking PGE restores re-sensitizes tumours cell-mediated immunity. Together, our work uncovers central stimulation, elucidates how oncogenic disrupts counter-regulation IFN-I, proposes rational combination therapies enhance immunotherapies.

Language: Английский

The hallmarks of cancer immune evasion DOI
Claudia Galassi, Timothy A. Chan, Ilio Vitale

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

Citations

57
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

et al.

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

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

Citations

53
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy DOI Creative Commons
Belén Toledo,

Linrui Zhu Chen,

María Paniagua-Sancho

et al.

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

Published: June 11, 2024

Abstract Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles growth, angiogenesis, regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 M2 subtypes based on their differentiation activities. macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while with an anti-inflammatory function protumoural regulators. highly versatile respond to stimuli from other constituents within (TME), such growth factors, cytokines, chemokines, enzymes. induce polarization towards one phenotype another, leading complex interactions TME components influencing both pro-tumour anti-tumour processes. This review comprehensively deeply covers literature origin well intricate interplay between TME, dual nature promoting pro- Moreover, delves primary pathways implicated macrophage polarization, examining diverse that regulate this process. role shaping functions macrophages. In addition, advantages limitations current clinical interventions reviewed, including enhancing TAM phagocytosis, inducing exhaustion, inhibiting recruitment, polarizing M1-like phenotype. conclusion, treatment strategies targeting precision medicine show promise, overcoming several obstacles is still necessary achieve accessible efficient immunotherapy.

Language: Английский

Citations

48
Macrophage polarization in the tumor microenvironment: Emerging roles and therapeutic potentials DOI Open Access
Wenru Zhang, Mengmeng Wang, Chonghao Ji

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116930 - 116930

Published: June 14, 2024

The tumor microenvironment (TME) is a combination of cells and indigenous host stroma, which consists tumor-infiltrating immune cells, endothelial fibroblasts, pericytes, non-cellular elements. Tumor-associated macrophages (TAMs) represent the major cell type are generally polarized into two functionally contradictory subtypes, namely classical activated M1 alternatively M2 macrophages. Macrophage polarization refers to how at given time space. interplay between TME macrophage can influence initiation progression, making TAM potential target for cancer therapy. Here, we review latest investigations on factors orchestrating in TME, affects perspectives modulating immunotherapy.

Language: Английский

Citations

28
A temporal perspective for tumor-associated macrophage identities and functions DOI
Camille Blériot, Garett Dunsmore, Direna Alonso‐Curbelo

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 747 - 758

Published: April 25, 2024

Language: Английский

Citations

21
Decoding the spatiotemporal heterogeneity of tumor-associated macrophages DOI Creative Commons

Xiangyuan Chu,

Yu Tian, Chao Lv

et al.

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

Published: July 27, 2024

Abstract Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial temporal heterogeneity of TAMs within microenvironment (TME), highlighting their diverse subtypes, origins, functions. Advanced technologies such as single-cell sequencing multi-omics have elucidated intricate interactions between other TME components, revealing mechanisms behind recruitment, polarization, distribution. Key findings demonstrate that support vascularization, promote epithelial-mesenchymal transition (EMT), modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing invasiveness metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways overcoming drug resistance. underscores potential targeting to develop innovative therapies, emphasizing need further research into characteristics functional roles TME.

Language: Английский

Citations

18
Defining myeloid-derived suppressor cells DOI
Leila Akkari, Ido Amit, Vincenzo Bronte

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(12), P. 850 - 857

Published: July 5, 2024

Citations

16
Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer DOI
Chikanori Tsutsumi, Kenoki Ohuchida,

Naoki Katayama

et al.

Gastric Cancer, Journal Year: 2024, Volume and Issue: 27(2), P. 248 - 262

Published: Jan. 13, 2024

Language: Английский

Citations

15
Targeting of TAMs: can we be more clever than cancer cells? DOI Creative Commons
Julia Kzhyshkowska, Jiaxin Shen, Irina Larionova

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1376 - 1409

Published: Nov. 8, 2024

АBSTRACT: With increasing incidence and geography, cancer is one of the leading causes death, reduced quality life disability worldwide. Principal progress in development new anticancer therapies, improving efficiency immunotherapeutic tools, personification conventional therapies needs to consider cancer-specific patient-specific programming innate immunity. Intratumoral TAMs their precursors, resident macrophages monocytes, are principal regulators tumor progression therapy resistance. Our review summarizes accumulated evidence for subpopulations number biomarkers, indicating predictive value clinical parameters carcinogenesis resistance, with a focus on solid cancers non-infectious etiology. We present state-of-the-art knowledge about tumor-supporting functions at all stages highlight recently identified by single-cell spatial analytical methods, that discriminate between tumor-promoting tumor-inhibiting TAMs, where both subtypes express combination prototype M1 M2 genes. focuses novel mechanisms involved crosstalk among epigenetic, signaling, transcriptional metabolic pathways TAMs. Particular attention has been given link cell metabolism epigenetic histone lactylation, which can be responsible unlimited protumoral Finally, we explain how interfere currently used therapeutics summarize most advanced data from trials, divide into four categories: inhibition TAM survival differentiation, monocyte/TAM recruitment tumors, functional reprogramming genetic enhancement macrophages.

Language: Английский

Citations

13
Immune Cell Migration to Cancer DOI Creative Commons
Allison Ryan, Minsoo Kim, Kihong Lim

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(10), P. 844 - 844

Published: May 16, 2024

Immune cell migration is required for the development of an effective and robust immune response. This elegant process regulated by both cellular environmental factors, with variables such as state, anatomical location, disease state that govern differences in patterns. In all cases, a major factor expression surface receptors their cognate ligands. Rapid adaptation to conditions partly depends on intrinsic factors affect cell’s ability adjust new environment. this review, we discuss myeloid lymphoid cells outline key determinants migration, including molecules adhesion, modes chemotaxis, specific chemokine signaling. Furthermore, summarize tumor-specific elements contribute trafficking cancer, while also exploring microenvironment can alter these dynamics within tumor pro antitumor fashion. Specifically, highlight importance secretome later aspects. review considers myriad impact trajectory cancer. We aim immunotherapeutic targets be harnessed achieve controlled tumors.

Language: Английский

Citations

12