Exploiting innate immunity for cancer immunotherapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

Pancreatic cancer: Advances and challenges DOI Creative Commons
Christopher J. Halbrook, Costas A. Lyssiotis, Marina Pasca di Magliano

et al.

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

Citations

563
Challenges and Opportunities for Pancreatic Cancer Immunotherapy DOI Creative Commons
Adham S. Bear, Robert H. Vonderheide, Mark H. O’Hara

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(6), P. 788 - 802

Published: Sept. 17, 2020

Language: Английский

Citations

443
Dendritic Cells and Their Role in Immunotherapy DOI Creative Commons
Alycia Gardner, Álvaro de Mingo Pulido, Brian Ruffell

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: May 21, 2020

Despite significant advances in the field of cancer immunotherapy, majority patients still do not benefit from treatment and must rely on traditional therapies. Dendritic cells have long been a focus immunotherapy due to their role inducing protective adaptive immunity, but vaccines shown limited efficacy past. With advent immune checkpoint blockade ability identify patient-specific neoantigens, new combinatorial therapies are being evaluated clinic. also emerging as critical regulators response with tumors. Understanding how augment function these intratumoral dendritic could offer approaches enhance addition improving cytotoxic targeted that partially dependent upon robust for efficacy. Here we will discuss specific cell subsets regulating anti-tumor response, well current status cell-based immunotherapies, order provide an overview future lines research clinical trials.

Language: Английский

Citations

395
Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer DOI
Nina G. Steele, Eileen S. Carpenter, Samantha B. Kemp

et al.

Nature Cancer, Journal Year: 2020, Volume and Issue: 1(11), P. 1097 - 1112

Published: Oct. 26, 2020

Language: Английский

Citations

359
Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma DOI Creative Commons

Yunzhen Qian,

Yitao Gong,

Zhiyao Fan

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Oct. 2, 2020

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by poor prognosis and high mortality rate. Genetic mutations altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified used to develop strategies that will selectively kill cancerous cells patients with PDAC. The realization of targeted therapies PDAC may summarized three approaches. First, because oncogenes play pivotal role tumorigenesis, inhibition dysregulated promising method (Table 3). Numerous researchers are developing target oncogenes, such KRAS, NRG1, NTRK related molecules, although most the results unsatisfactory. Accordingly, emerging being developed including simultaneously inhibiting multiple molecules or pathways, modification mutant residues small RNA interference. Second, have attempted reactivate inactivated tumour suppressors modulate molecules. TP53, CDKN2A SMAD4 major involved Advances been achieved clinical preclinical trials targeting genes, further investigations warranted. TGF-β-SMAD4 signalling pathway plays dual tumorigenesis participates mediating tumour-stroma crosstalk modulating microenvironment (TME); thus, subtyping pancreatic cancer according mutation status precision oncology technique. Finally, genes KDM6A BRCA vital roles maintaining structural stability physiological functions normal chromosomes deficient some PDAC, thus serving potential for correcting deficiencies precisely killing cells. Recent trials, POLO (Pancreas Cancer Olaparib Ongoing) trial, reported encouraging outcomes. In addition genetic event-guided treatment, immunotherapies chimeric antigen receptor T (CAR-T), antibody-drug conjugates, immune checkpoint inhibitors also exhibit tumours precisely, value treatments still limited. this review, we focus on recent advances predict future trend

Language: Английский

Citations

250
Cell death in pancreatic cancer: from pathogenesis to therapy DOI
Xin Chen, Herbert J. Zeh, Rui Kang

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(11), P. 804 - 823

Published: July 30, 2021

Language: Английский

Citations

242
A reservoir of stem-like CD8 + T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response DOI
Kelli A. Connolly, Manik Kuchroo, Aarthi Venkat

et al.

Science Immunology, Journal Year: 2021, Volume and Issue: 6(64)

Published: Sept. 2, 2021

Tumor-specific CD8 + T cells in stable tumor-draining lymph node reservoir are clonally and developmentally related to those tumors.

Language: Английский

Citations

241
The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives DOI Creative Commons
Shun Wang, Yan Zheng, Yang Feng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 5, 2021

Abstract Pancreatic cancer is an increasingly common cause of mortality with a tight correspondence between disease and incidence. Furthermore, it usually diagnosed at advanced stage very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, dense stromal environment associated pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into biology genetics has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how biological features reprogramming as well tumor microenvironment regulate development progression. We further discuss potential biomarkers for diagnosis, prediction, surveillance based on novel liquid biopsies. also outline recent advances in defining subtypes subtype-specific responses preclinical models. Finally, prospects challenges therapeutics.

Language: Английский

Citations

237
Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance DOI Creative Commons
Mara H. Sherman, Gregory L. Beatty

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 123 - 148

Published: Sept. 21, 2022

Pancreatic ductal adenocarcinoma (PDAC) features a prominent stromal microenvironment with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology treatment resistance. Recent advances in tissue imaging capabilities, single-cell analytics, modeling have shed light on organizing principles shape the complexity of PDAC tumors. These insights into functional dependencies coordinate cancer cell relationships exist between cells extracellular matrix components present tumors are expected to unveil therapeutic vulnerabilities. We review recent field discuss current understandings mechanisms by which tumor shapes pathogenesis therapy

Language: Английский

Citations

206
Tumor-infiltrating dendritic cell states are conserved across solid human cancers DOI Creative Commons
Genevieve M. Gerhard, Ruben Bill, Marius Messemaker

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 218(1)

Published: Dec. 18, 2020

Dendritic cells (DCs) contribute a small fraction of the tumor microenvironment but are emerging as an essential antitumor component based on their ability to foster T cell immunity and immunotherapy responses. Here, we discuss our expanding view DC heterogeneity in human tumors, revealed with meta-analysis single-cell transcriptome profiling studies. We further examine tumor-infiltrating states that conserved across patients, cancer types, species consider fundamental clinical relevance these findings. Finally, provide outlook research opportunities explore mechanisms governing behavior functions.

Language: Английский

Citations

190