Depicting the cellular complexity of pancreatic adenocarcinoma by Imaging Mass Cytometry: focus on cancer-associated fibroblasts DOI Creative Commons
Marco Erreni, Maria Rita Fumagalli,

Raffaella D’Anna

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 7, 2024

Introduction Pancreatic ductal adenocarcinoma (PDAC) represents the complexity of interaction between cancer and cells tumor microenvironment (TME). Immune affect cell behavior, thus driving progression. Cancer-associated fibroblasts (CAFs) are responsible desmoplastic fibrotic reaction by regulating deposition remodeling extracellular matrix (ECM). As tumor-promoting abundant in PDAC ECM, CAFs represent promising targets for novel anticancer interventions. However, relevant clinical trials hampered lack specific markers elusive differences among CAF subtypes. Indeed, while single-cell transcriptomic analyses have provided important information on cellular constituents PDACs related molecular pathways, studies based identification protein tissues aimed at identifying subtypes new result incomplete. Methods Herein, we applied multiplexed Imaging Mass Cytometry (IMC) resolution 8 human to depict composing cells, profiling immune endothelial (ECs), as well endocrine cells. Results We focused characterizing up 19 clusters distinguished phenotype, spatiality, with report evidence that (CAFs 10 11) predominantly enriched tumor-stroma interface closely associated expressing different combinations FAP, podoplanin cadherin-11, were a higher level CA19-9. Moreover, identified subsets FAP + /cadherin-11 patients negative prognosis. Discussion The present study provides general insights into defining phenotypic heterogeneities spatial distributions CAFs, suggesting functions their microenvironment.

Language: Английский

Current and future immunotherapeutic approaches in pancreatic cancer treatment DOI Creative Commons
Pooya Farhangnia, Hossein Khorramdelazad, Hamid Nickho

et al.

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

Published: June 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Language: Английский

Citations

34
Pancreatic cancer environment: from patient-derived models to single-cell omics DOI

Ao Gu,

Jiatong Li,

Shimei Qiu

et al.

Molecular Omics, Journal Year: 2024, Volume and Issue: 20(4), P. 220 - 233

Published: Jan. 1, 2024

This review initially presents relevant patient-derived models, including PDXs, PDOs, and PDEs. Subsequently, a comprehensive summary of single-cell analyses conducted on these models is provided.

Language: Английский

Citations

24
Advances in spatial transcriptomics and its applications in cancer research DOI Creative Commons
Huazhe Yang,

Yuanli Zuo,

Gang Li

et al.

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

Published: June 20, 2024

Abstract Malignant tumors have increasing morbidity and high mortality, their occurrence development is a complicate process. The of sequencing technologies enabled us to gain better understanding the underlying genetic molecular mechanisms in tumors. In recent years, spatial transcriptomics been developed rapidly allow quantification illustration gene expression context tissues. Compared with traditional technologies, not only detect levels cells, but also inform location genes within tissues, cell composition biological interaction between cells. Here we summarize tools its application cancer research. We discuss limitations challenges current approaches, as well future prospects.

Language: Английский

Citations

24
Dysbiosis–NK Cell Crosstalk in Pancreatic Cancer: Toward a Unified Biomarker Signature for Improved Clinical Outcomes DOI Open Access
Sara Fanijavadi, Lars Henrik Jensen

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 730 - 730

Published: Jan. 16, 2025

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, primarily due to its immunosuppressive tumor microenvironment (TME), which contributes treatment resistance. Recent research shows that the microbiome, including microbial communities in oral cavity, gut, bile duct, and intratumoral environments, plays a key role PDAC development, imbalances (dysbiosis) promoting inflammation, progression, therapy resistance, side effects. Microbial metabolites can also affect immune cells, especially natural killer (NK) are vital for surveillance, response treatment-related Dysbiosis NK cell function, leading resistance We propose combined biomarker approach, integrating microbiome composition profiles, help predict effects, enabling more personalized therapies. This review examines how dysbiosis dysfunction discusses strategies (e.g., antibiotics, probiotics, vaccines) modulate enhance function. Targeting could activity, improve effectiveness of treatments, reduce However, further needed develop unified cell–microbiome interaction-based biomarkers precise effective patient outcomes.

Language: Английский

Citations

1
The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy DOI
Marc Hilmi, Matthieu Delaye,

Milena Muzzolini

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(12), P. 1129 - 1142

Published: Oct. 19, 2023

Language: Английский

Citations

22
Cellular collusion: cracking the code of immunosuppression and chemo resistance in PDAC DOI Creative Commons
Chiara Musiu,

Francesca Lupo,

Antonio De Agostini

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 16, 2024

Despite the efforts, pancreatic ductal adenocarcinoma (PDAC) is still highly lethal. Therapeutic challenges reside in late diagnosis and establishment of peculiar tumor microenvironment (TME) supporting outgrowth. This stromal landscape heterogeneous between patients even same patient. The organization functional sub-TME with different cellular compositions provides evolutive advantages sustains therapeutic resistance. Tumor progressively establishes a TME that can suit its own needs, including proliferation, stemness invasion. Cancer-associated fibroblasts immune cells, main non-neoplastic components, follow soluble factors-mediated neoplastic instructions synergize to promote chemoresistance surveillance destruction. Unveiling heterotypic stromal-neoplastic interactions thus pivotal breaking this synergism promoting reprogramming toward an anti-tumor milieu, improving efficacy conventional immune-based therapies. We underscore recent advances characterization fibroblast components or dampening cancer progression, as well novel multi-omic technologies current knowledge PDAC biology. Finally, we put into context how clinic will translate acquired design new-generation clinical trials final aim outcome patients.

Language: Английский

Citations

6
Spatial transcriptomics in cancer research and potential clinical impact: a narrative review DOI Creative Commons
Michael A. Cilento, Christopher J. Sweeney, Lisa M. Butler

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(6)

Published: June 8, 2024

Spatial transcriptomics (ST) provides novel insights into the tumor microenvironment (TME). ST allows quantification and illustration of gene expression profiles in spatial context tissues, including both cancer cells which they are found. In research, has already provided metastasis, prognosis, immunotherapy responsiveness. The clinical precision oncology application next-generation sequencing (NGS) RNA profiling tumors relies on bulk methods that lack context. ability to preserve information is now possible, as it us capture heterogeneity multifocality. this narrative review, we summarize oncology, discuss clinic, review available research methods, seqFISH, MERFISH (Vizgen), CosMx SMI (NanoString), Xenium (10x), Visium Stereo-seq (STOmics), GeoMx DSP (NanoString). We then current literature with a focus solid organized by type. Finally, conclude addressing an important question: how will ultimately help patients cancer?

Language: Английский

Citations

6
Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer DOI Creative Commons
Yifan Fu, Jinxin Tao, Tao Liu

et al.

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

Published: July 9, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled development immunotherapeutic targeted strategies promising future. The emergence single-cell sequencing mass spectrometry technologies, coupled spatial omics, collectively revealed heterogeneity TME from multiomics perspective, outlined trajectories cell lineages, important functions previously underrated myeloid cells stroma cells. Concurrently, these findings necessitated more refined annotations biological at cluster or level. Precise identification all clusters urgently needed to determine whether they have been investigated adequately identify target antitumor potential, design compatible treatment strategies, resistance. Here, we summarize recent research level, an unbiased focus potential classification bases every cellular component within TME, look forward prospects integrating data retrospectively reusing bulk data, hoping provide new insights into TME.

Language: Английский

Citations

6
Emerging trends and hot topics in the application of multi-omics in drug discovery: A bibliometric and visualized study DOI Creative Commons
Ziheng Wang, Yang Zhao, Long Zhang

et al.

Current Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: 21(1), P. 20 - 32

Published: Dec. 1, 2024

Language: Английский

Citations

5
Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer DOI
Jonathan H. Sussman, Nathalia Kim, Samantha B. Kemp

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(14), P. 2364 - 2376

Published: May 2, 2024

Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral heterogeneity in PDAC. this study, we investigated microenvironment PDAC applying imaging mass cytometry using 26-antibody panel on 35 regions interest across 9 patients, capturing more than 140,000 single The approach distinguished major types, including multiple populations lymphoid myeloid cells, endocrine stromal endothelial Evaluation cellular neighborhoods identified 10 distinct domains, immune tumor-enriched environments as well niche. Focused analysis revealed differential vasculature domains wherein proliferation occurs. Importantly, was closely associated with population CD44-expressing macrophages enriched for proangiogenic gene signature. Taken together, study provides insights into suggests role shaping Significance: Imaging cancers composed neighborhoods, expressing high levels CD44

Language: Английский

Citations

4