Pancreatic cancer: Advances and challenges

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1729 - 1754

Published: April 1, 2023

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. tumors are characterized by a complex microenvironment that orchestrates metabolic alterations supports milieu interactions among various cell types within this niche. In review, we highlight foundational studies driven our understanding these processes. We further discuss recent technological advances continue to expand complexity. posit clinical translation research endeavors will enhance currently dismal survival rate recalcitrant disease.

Language: Английский

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Single-cell profiling to explore pancreatic cancer heterogeneity, plasticity and response to therapy

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(4), P. 454 - 467

Published: March 23, 2023

Language: Английский

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Tumor immune microenvironment-based therapies in pancreatic ductal adenocarcinoma: time to update the concept

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Jan. 2, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. The tumor immune microenvironment (TIME) formed by interactions among cancer cells, cancer-associated fibroblasts (CAF), and extracellular matrix (ECM) components drives PDAC in a more immunosuppressive direction: this major cause therapy resistance poor prognosis. In recent years, research has advanced our understanding signaling mechanism which TIME interact with evolution immunophenotyping. Through revolutionary technologies such as single-cell sequencing, we have gone from simply classifying PDACs “cold” “hot” to comprehensive approach immunophenotyping that considers all cells components. This key improving clinical efficacy treatments. review, elaborate on various PDAC, mechanisms underlying their interactions, latest into A deep these network will contribute effective combination TIME-based therapeutic approaches, checkpoint inhibitors (ICI), adoptive cell therapy, therapies targeting myeloid CAF reprogramming, stromal normalization. By selecting appropriate integrated based precise immunophenotyping, significant advances future treatment are possible.

Language: Английский

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From Machine Learning to Patient Outcomes: A Comprehensive Review of AI in Pancreatic Cancer

Diagnostics, Journal Year: 2024, Volume and Issue: 14(2), P. 174 - 174

Published: Jan. 12, 2024

Pancreatic cancer is a highly aggressive and difficult-to-detect with poor prognosis. Late diagnosis common due to lack of early symptoms, specific markers, the challenging location pancreas. Imaging technologies have improved diagnosis, but there still room for improvement in standardizing guidelines. Biopsies histopathological analysis are tumor heterogeneity. Artificial Intelligence (AI) revolutionizes healthcare by improving treatment, patient care. AI algorithms can analyze medical images precision, aiding disease detection. also plays role personalized medicine analyzing data tailor treatment plans. It streamlines administrative tasks, such as coding documentation, provides assistance through chatbots. However, challenges include privacy, security, ethical considerations. This review article focuses on potential transforming pancreatic care, offering diagnostics, treatments, operational efficiency, leading better outcomes.

Language: Английский

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Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma

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

Published: July 24, 2023

Immunosuppression is a hallmark of pancreatic ductal adenocarcinoma (PDAC), contributing to early metastasis and poor patient survival. Compared the localized tumors, current standard-of-care therapies have failed improve survival patients with metastatic PDAC, that necessecitates exploration novel therapeutic approaches. While immunotherapies such as immune checkpoint blockade (ICB) vaccines emerged promising treatment modalities in certain cancers, limited responses been achieved PDAC. Therefore, specific mechanisms regulating response immunotherapy must be explored. The immunosuppressive microenvironment driven by oncogenic mutations, tumor secretome, non-coding RNAs, microbiome persists throughout PDAC progression, allowing neoplastic cells grow locally metastasize distantly. escaping host surveillance are unique molecular, immunological, metabolic characteristics. Following chemokine exosomal guidance, these organ-specific pre-metastatic niches (PMNs) constituted local resident cells, stromal fibroblasts, suppressive metastasis-associated macrophages, neutrophils, myeloid-derived suppressor cells. differs from primary tumors cell composition, functionality, metabolism. Thus far, multiple molecular pathways, distinct identified dampen effector functions, confounding This review describes major immunoregulatory pathways contribute progression limit outcomes Overall, we highlight vulnerabilities attributable factors discuss whether targeting immunological "hot spots" could immunotherapies.

Language: Английский

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Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs

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

Published: Nov. 14, 2023

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cell signals, TAMs exhibit unparalleled adaptability, aligning with dynamic milieu. Their roles span from promoting growth and angiogenesis modulating metastasis. While substantial research has explored fundamentals of TAMs, comprehending their adaptive behavior, leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, complex orchestration cytokines chemokines determining functions. We highlight complexities TAM-targeted focusing on adaptability potential variability in therapeutic outcomes. Moreover, we discuss synergy integrating TAM-focused strategies established treatments, such as chemotherapy, immunotherapy. Emphasis is laid pioneering methods like reprogramming immunotherapy adoption single-cell technologies precision intervention. synthesis seeks shed light TAMs’ multifaceted cancer, pinpointing prospective pathways transformative enhancing modalities oncology.

Language: Английский

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Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors

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

Published: March 13, 2024

Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding transformation to 'hot' is essential developing effective cancer treatments. Furthermore, tumor profiling critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success immunotherapy relies on T cells' ability recognize eliminate cells. In absence cell infiltration leads ineffectiveness ICI therapy. Addressing these challenges, especially impairment activation homing, crucial enhance therapy's efficacy. Concurrently, strategies convert into ones, including boosting adoptive therapies such as cell-recruiting bispecific antibodies Chimeric Antigen Receptor (CAR) cells, are under extensive exploration. Thus, identifying key factors that impact vital creating treatments targeting tumors.

Language: Английский

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TGFβ-specific T cells induced by a TGFβ-derived immune modulatory vaccine both directly and indirectly modulate the phenotype of tumor-associated macrophages and fibroblasts

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(2), P. e008405 - e008405

Published: Feb. 1, 2024

The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive. We recently developed a transforming growth factor (TGF)β-based immune modulatory vaccine that controlled in murine model by targeting immunosuppression and desmoplasia the TME. found treatment with TGFβ not only reduced percentage M2-like tumor-associated macrophages (TAMs) cancer-associated fibroblasts (CAFs) but polarized CAFs away from myofibroblast-like phenotype. However, whether properties on TAM CAF phenotypes are direct consequence recognition subsequent these subsets TGFβ-specific T cells or an indirect overall modulation induced within TME remains unknown. Recognition M2 fibroblast was assessed ELISpot flow cytometry. effects cell were evaluated culturing tumor-conditioned media isolated spleen mice treated control vaccine, respectively. Changes phenotype cytometry Bio-Plex multiplex system (Luminex). can recognize fibroblasts. Furthermore, we demonstrated be directly modulated as well indirectly result immune-modulatory TAMs tend to have tumor-promoting functions, harbor immunosuppressive linked decreased survival when they In addition, create stiff extracellular matrix restricts infiltration, impeding effectiveness therapies desmoplastic tumors, such ductal adenocarcinoma. Reducing exclusion tumors TGFβ-based emerges innovative strategy for generation more favorable environment immune-based therapies, checkpoint inhibitors.

Language: Английский

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Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

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

Published: May 2, 2024

Pancreatic cancer is a highly aggressive malignant tumor, that becoming increasingly common in recent years. Despite advances intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted the overall survival rate has not significantly improved patients with pancreatic cancer. This may be attributed to insidious onset, unknown pathophysiology, poor prognosis of disease. It therefore essential identify develop more effective safer treatments for Tumor immunotherapy new fourth pillar anti-tumor therapy after chemotherapy. Significant progress made use wide variety tumors years; breakthrough also been review describes immune checkpoint inhibitors, vaccines, adoptive cell oncolytic virus, matrix-depletion therapies At same time, some potential biomarkers combinations are discussed. The molecular mechanisms various immunotherapies have elucidated, their clinical applications highlighted. current challenges associated proposed strategies hold promise overcoming these limitations discussed, aim offering insights into

Language: Английский

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Precision treatment of pancreatic ductal adenocarcinoma

Cancer Letters, Journal Year: 2024, Volume and Issue: 585, P. 216636 - 216636

Published: Jan. 25, 2024

Language: Английский

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