Reprogramming Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD1 Therapy.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
27 Jan 2023
Historique:
pubmed: 8 2 2023
medline: 8 2 2023
entrez: 7 2 2023
Statut: epublish

Résumé

Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Anti-PD-L1 immunotherapy combined with gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers, but responses are seen only in a minority of patients. Here, we studied the roles of anti-PD1 and anti-CTLA-4 immune checkpoint blockade (ICB) therapies when combined with gemcitabine/cisplatin and the mechanisms of treatment benefit in orthotopic murine ICC models. We evaluated the effects of the combined treatments on ICC vasculature and immune microenvironment using flow cytometry analysis, immunofluorescence, imaging mass cytometry, RNA-sequencing, qPCR, and

Identifiants

DOI: 10.1101/2023.01.26.525680 PMID: 36747853 PMC: PMC9901023
pubmed: 36747853
doi: 10.1101/2023.01.26.525680
pmc: PMC9901023
pii:
doi:

Types de publication

Preprint

Langues

eng

Déclaration de conflit d'intérêts

Competing interests: RKJ reports grants from Jane’s Trust Foundation, Niles Albright Research Foundation, National Foundation for Cancer Research, and Ludwig Center at Harvard during the conduct of the study; personal fees from BMS, Cur Therapeutics, Elpis Biopharmaceuticals, Innocoll Pharmaceuticals, SPARC, SynDevRx, Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, Tekla World Healthcare Fund; owns equity in Accurius Therapeutics, Enlight Biosciences, SynDevRx; and received grants from Boehringer Ingelheim and Sanofi. DGD received consultant fees from Innocoll Pharmaceuticals and research grants from Exelixis, Bayer, BMS, and Surface Oncology. No reagents from these companies were used in this study.

Auteurs

Jiang Chen (J)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Zohreh Amoozgar (Z)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Xin Liu (X)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School; 185 Cambridge Street, Simches Building, CPZN-4216, Boston, MA 02114, USA.

Shuichi Aoki (S)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Zelong Liu (Z)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Sarah Shin (S)

Department of Medicine, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 401 N. Broadway, Baltimore, MD 21231, USA.

Aya Matsui (A)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Zhangya Pu (Z)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Pin-Ji Lei (PJ)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Meenal Datta (M)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Lingling Zhu (L)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Zhiping Ruan (Z)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Lei Shi (L)

Department of Medicine, Massachusetts General Hospital and Harvard Medical School; 185 Cambridge Street, Simches Building, CPZN-4216, Boston, MA 02114, USA.

Daniel Staiculescu (D)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Koetsu Inoue (K)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Lance L Munn (LL)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Dai Fukumura (D)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Peigen Huang (P)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Nabeel Bardeesy (N)

Department of Medicine, Massachusetts General Hospital and Harvard Medical School; 185 Cambridge Street, Simches Building, CPZN-4216, Boston, MA 02114, USA.

Won Jin Ho (WJ)

Department of Medicine, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 401 N. Broadway, Baltimore, MD 21231, USA.

Rakesh K Jain (RK)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Dan G Duda (DG)

Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Classifications MeSH