Li, Jiayun, Moresco, Philip, Fearon, Douglas T (July 2024) Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America, 121 (29). e2403917121. ISSN 0027-8424 (Public Dataset)
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Abstract
Pancreatic ductal adenocarcinoma (PDA) is a potentially lethal disease lacking effective treatments. Its immunosuppressive tumor microenvironment (TME) allows it to evade host immunosurveillance and limits response to immunotherapy. Here, using the mouse KRT19-deficient (sgKRT19-edited) PDA model, we find that intratumoral accumulation of natural killer T (NKT) cells is required to establish an immunologically active TME. Mechanistically, intratumoral NKT cells facilitate type I interferon (IFN) production to initiate an antitumor adaptive immune response, and orchestrate the intratumoral infiltration of T cells, dendritic cells, natural killer cells, and myeloid-derived suppressor cells. At the molecular level, NKT cells promote the production of type I IFN through the interaction of their CD40L with CD40 on myeloid cells. To evaluate the therapeutic potential of these observations, we find that administration of folinic acid to mice bearing PDA increases NKT cells in the TME and improves their response to anti-PD-1 antibody treatment. In conclusion, NKT cells have an essential role in the immune response to mouse PDA and are potential targets for immunotherapy.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms organism description > animal diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > drugs and therapies > Immunotherapy organism description > animal > mammal organism description > animal > mammal > rodent > mouse diseases & disorders > cancer > cancer types > pancreatic cancer organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Fearon lab CSHL Cancer Center Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 16 July 2024 |
| Date Deposited: | 15 Jul 2024 13:23 |
| Last Modified: | 01 Oct 2024 17:44 |
| PMCID: | PMC11260137 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/41601 |
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