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

The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer DOI
William A. Freed-Pastor,

Laurens J. Lambert,

Zackery A. Ely

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(10), P. 1342 - 1360.e14

Published: Aug. 5, 2021

Language: Английский

Citations

188
Translational advances in pancreatic ductal adenocarcinoma therapy DOI Open Access
Abdel Hosein, Stephanie K. Dougan, Andrew J. Aguirre

et al.

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(3), P. 272 - 286

Published: March 29, 2022

Language: Английский

Citations

176
The role of dendritic cells in cancer and anti-tumor immunity DOI
Ariel E. Marciscano, Niroshana Anandasabapathy

Seminars in Immunology, Journal Year: 2021, Volume and Issue: 52, P. 101481 - 101481

Published: Feb. 1, 2021

Language: Английский

Citations

170
Regulation and modulation of antitumor immunity in pancreatic cancer DOI
Joshua Leinwand, George Miller

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(10), P. 1152 - 1159

Published: Aug. 17, 2020

Language: Английский

Citations

167
Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis DOI Creative Commons
Jeffrey H. Lin,

Austin P. Huffman,

Max M. Wattenberg

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(8)

Published: May 26, 2020

Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily invasive cancer. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre-driven (KPC) mouse model is systemic and progressive, driven by increased apoptosis, results suboptimal up-regulation T cell-polarizing cytokines during maturation. The underlying mechanism linked elevated IL-6 concomitant with neoplasia. Neutralization vivo ameliorates rescuing abundance tumor-bearing mice. CD8+ cell response vaccination impaired as a result dysregulation. Yet, combination therapy CD40 agonist Flt3 ligand restores normal levels, decreases repairs maturation drive superior control tumor outgrowth. Our study therefore reveals unexpectedly early onset dysregulation carcinogenesis suggests therapeutically tractable strategies toward repair.

Language: Английский

Citations

152
Targeting the CCL2/CCR2 Axis in Cancer Immunotherapy: One Stone, Three Birds? DOI Creative Commons

Liyang Fei,

Xiaochen Ren,

Haijia Yu

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 3, 2021

CCR2 is predominantly expressed by monocytes/macrophages with strong proinflammatory functions, prompting the development of antagonists to dampen unwanted immune responses in inflammatory and autoimmune diseases. Paradoxically, CCR2-expressing monocytes/macrophages, particularly tumor microenvironments, can be strongly immunosuppressive. Thus, targeting recruitment immunosuppressive tumors antagonism has recently been investigated as a strategy modify microenvironment enhance anti-tumor immunity. We present here that beneficial effects setting extend beyond blocking chemotaxis suppressive myeloid cells. Signaling within CCL2/CCR2 axis shows underappreciated on cell survival function polarization. Apart from cells, T cells are also known express CCR2. Nevertheless, tissue homing Treg among populations preferentially affected deficiency. Further, signaling directly enhances functional potency. although Tregs not sole type expressing CCR2, net outcome favors arm responses. Finally, contributes survival/growth invasion/metastasis many types bearing Together, links two main multiple mechanisms. Such CCR2-assoicated network further entangled paracrine autocrine Strategies target cancer therapy view three CCR2-expessing discussed.

Language: Английский

Citations

148
Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer DOI Creative Commons
Daniel Cui Zhou, Reyka G. Jayasinghe, Siqi Chen

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(9), P. 1390 - 1405

Published: Aug. 22, 2022

Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, transcriptomics cellular imaging. Subpopulations of tumor cells exhibited signatures proliferation, KRAS signaling, cell stress epithelial-to-mesenchymal transition. Mapping mutations copy number events distinguished populations normal transitional cells, including acinar-to-ductal metaplasia pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution transcriptomic data identified subpopulations distinct histological features. showed coordinated expression TIGIT in exhausted regulatory T Nectin cells. Chemo-resistant contain threefold enrichment inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals deeper understanding the intricate substructure tumors could help improve therapy for this disease.

Language: Английский

Citations

136
Therapeutic developments in pancreatic cancer DOI
Zilun Hu, Eileen M. O’Reilly

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 21(1), P. 7 - 24

Published: Oct. 5, 2023

Language: Английский

Citations

135
Neoadjuvant Selicrelumab, an Agonist CD40 Antibody, Induces Changes in the Tumor Microenvironment in Patients with Resectable Pancreatic Cancer DOI Creative Commons
Katelyn T. Byrne, Courtney B. Betts, Rosemarie Mick

et al.

Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 27(16), P. 4574 - 4586

Published: June 10, 2021

CD40 activation is a novel clinical opportunity for cancer immunotherapy. Despite numerous active trials with agonistic monoclonal antibodies (mAb), biological effects and treatment-related modulation of the tumor microenvironment (TME) remain poorly understood.

Language: Английский

Citations

129
Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes DOI Creative Commons
Samuel I. Kim,

Christopher R. Cassella,

Katelyn T. Byrne

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 11

Published: Feb. 1, 2021

Cancer immunotherapy has revolutionized the treatment landscape in medical oncology, but its efficacy been variable across patients. Biomarkers to predict such differential response include cytotoxic T lymphocyte infiltration, tumor mutational burden, and microsatellite instability. A growing number of studies also suggest that baseline or size, predicts immunotherapy. In this review, we discuss changes immune profile therapeutic responses occur with increasing size. We overview approaches reduce burden favorably modulate microenvironment larger tumors.

Language: Английский

Citations

123