Targeting Hsp70 Immunosuppressive Signaling Axis with Lipid Nanovesicles: A Novel Approach to Treat Pancreatic Cancer DOI Open Access
Ahmet Kaynak,

Subrahmanya Vallabhapurapu,

Eric P. Smith

и другие.

Cancers, Год журнала: 2025, Номер 17(7), С. 1224 - 1224

Опубликована: Апрель 4, 2025

Despite many efforts to effectively treat PDAC, PDAC carries one of the highest mortality rates all major cancers. Thus, there is a critical unmet need develop novel approaches improve clinical outcome PDAC. It well known that cancers, including generate local TME allows cancer escape normal immune surveillance. Phosphatidylserine (PS), negatively charged phospholipid abundant on cell membrane and with actions promote secretion immunomodulatory proteins, may provide mechanism regulate TME. This study explored possibility. MΦ differentiation polarization were assessed by Western blotting flow cytometric approaches. PS exposure surface markers analyzed cytometry. Protein-protein protein-lipid interactions immunofluorescence enzyme-linked immunosorbent assay (ELISA). Phospholipid SapC-DOPG treatment employed assess target protein functions in polarization, tumor growth, survival subcutaneous orthotopic models. The PK-PD safety tested mouse Our studies show secretes Hsp70 stimulates immunosuppressive M2 phenotype. We found high cells correlates increased associated higher activity vitro vivo. Furthermore, blocking cell-secreted reverses suppression reduces growth. These preclinical results reveal immunotherapeutic approach potentially humans.

Язык: Английский

Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets DOI Open Access

Miguel L. Rufail,

Rosaria Bassi, Paola Giussani

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1056 - 1056

Опубликована: Янв. 26, 2025

Cancer biology revolves around understanding how cells undergo uncontrolled proliferation leading to the formation of malignant tumors. Key aspects include self-sufficiency in growth signals, lack response signals inhibition, evasion apoptosis, sustained angiogenesis, immune response, capacity invade and metastasize, alterations cellular metabolism. A vast amount research, which is exponentially growing, over past few decades highlights role sphingolipids cancer. They act not only as structural membrane components but also bioactive molecules that regulate cell fate different physio-pathological conditions. In cancer, sphingolipid metabolism dysregulated, contributing tumor progression, metastasis, drug resistance. this review, we outline impact sphingosine-1-phosphate (S1P) a key We give an overview its summarizing S1P intracellular extracellular mediator through specific plasma receptors cancers. describe previous findings on disruption balance between ceramide (Cer) common cancer can contribute tumorigenesis resistance chemotherapy. finally consider potential targeting metabolic pathways well transporters promising therapeutic approach treatments.

Язык: Английский

Процитировано

1
Targeting Hsp70 Immunosuppressive Signaling Axis with Lipid Nanovesicles: A Novel Approach to Treat Pancreatic Cancer DOI Open Access
Ahmet Kaynak,

Subrahmanya Vallabhapurapu,

Eric P. Smith

и другие.

Cancers, Год журнала: 2025, Номер 17(7), С. 1224 - 1224

Опубликована: Апрель 4, 2025

Despite many efforts to effectively treat PDAC, PDAC carries one of the highest mortality rates all major cancers. Thus, there is a critical unmet need develop novel approaches improve clinical outcome PDAC. It well known that cancers, including generate local TME allows cancer escape normal immune surveillance. Phosphatidylserine (PS), negatively charged phospholipid abundant on cell membrane and with actions promote secretion immunomodulatory proteins, may provide mechanism regulate TME. This study explored possibility. MΦ differentiation polarization were assessed by Western blotting flow cytometric approaches. PS exposure surface markers analyzed cytometry. Protein-protein protein-lipid interactions immunofluorescence enzyme-linked immunosorbent assay (ELISA). Phospholipid SapC-DOPG treatment employed assess target protein functions in polarization, tumor growth, survival subcutaneous orthotopic models. The PK-PD safety tested mouse Our studies show secretes Hsp70 stimulates immunosuppressive M2 phenotype. We found high cells correlates increased associated higher activity vitro vivo. Furthermore, blocking cell-secreted reverses suppression reduces growth. These preclinical results reveal immunotherapeutic approach potentially humans.

Язык: Английский

Процитировано

0