ReferenceID 1976

The combination of gemcitabine and ginsenoside Rh2 enhances the immune function of dendritic cells against pancreatic cancer via the CARD9-BCL10-MALT1 / NF-κB pathway

Clin Immunol

Cold tumor immune microenvironment (TIME) of pancreatic cancer (PC) with minimal dendritic cell (DC) and T cell infiltration can result in insufficient immunotherapy and chemotherapy. While gemcitabine (GEM) is a first-l

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Reference Id
1976
Evidence Id
18566
Core Evidence Id
18566
Source Reference Id
3973
Herb2 Reference Id
HBREF004770
Subject Paper Key
HBIN027764_36581220
Pubmed Id
36581220
Doi
10.1016/j.clim.2022.109217
Paper Title
The combination of gemcitabine and ginsenoside Rh2 enhances the immune function of dendritic cells against pancreatic cancer via the CARD9-BCL10-MALT1 / NF-κB pathway
Paper Abstract
Cold tumor immune microenvironment (TIME) of pancreatic cancer (PC) with minimal dendritic cell (DC) and T cell infiltration can result in insufficient immunotherapy and chemotherapy. While gemcitabine (GEM) is a first-line chemotherapeutic drug for PC, its efficacy is reduced by immunosuppression and drug resistance. Ginsenoside Rh2 (Rh2) is known to have anti-cancer and immunomodulatory properties. Combining GEM with Rh2 may thus overcome immunosuppression and induce lasting anti-tumor immunity in PC. Here, we showed that after GEM-Rh2 therapy, there was significantly greater tumor infiltration by DCs. Caspase recruitment domain-containing protein 9 (CARD9), a central adaptor protein, was strongly up-regulated DCs with GEM-Rh2 therapy and promoted anti-tumor immune responses by DCs. CARD9 was found to be a critical target for Rh2 to enhance DC function. However, GEM-Rh2 treatment did not achieve the substantial anti-PC efficacy in CARD9 -/- mice as in WT mice. The adoptive transfer of WT DCs to DC-depleted PC mice treated with GEM-Rh2 elicited strong anti-tumor immune responses, although CARD9 -/- DCs were less effective than WT DCs. Our results showed that GEM-Rh2 may reverse cold TIME by enhancing tumor immunogenicity and decreasing the levels of immunosuppressive factors, reactivating DCs via the CARD9-BCL10-MALT1/ NF-κB pathway. Our findings suggest a potentially feasible and safe treatment strategy for PC, with a unique mechanism of action. Thus, Rh2 activation of DCs may remodel the cold TIME and optimize GEM chemotherapy for future therapeutic use.
Journal
Clin Immunol
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal & Cell Experiment
Phenotype Related
Cold Tumor; Tumor; Pancreatic Cancer
Paper Title Cn
Paper Title En
The combination of gemcitabine and ginsenoside Rh2 enhances the immune function of dendritic cells against pancreatic cancer via the CARD9-BCL10-MALT1 / NF-κB pathway
Bilingual Status
semi_complete