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BTLA+CD200+ B cells dictate the divergent immune landscape and immunotherapeutic resistance in metastatic vs. primary pancreatic cancer.
Diskin, Brian; Adam, Salma; Soto, Gustavo Sanchez; Liria, Miguel; Aykut, Berk; Sundberg, Belen; Li, Eric; Leinwand, Joshua; Chen, Ruonan; Kim, Mirhee; Salas, Ruben D; Cassini, Marcelo F; Buttar, Chandan; Wang, Wei; Farooq, Mohammad Saad; Shadaloey, Sorin A A; Werba, Gregor; Fnu, Amreek; Yang, Fan; Hirsch, Carolina; Glinski, John; Panjwani, Angilee; Weitzner, Yael; Cohen, Deirdre; Asghar, Usman; Miller, George.
Affiliation
  • Diskin B; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Adam S; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Soto GS; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Liria M; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Aykut B; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Sundberg B; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Li E; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Leinwand J; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Chen R; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Kim M; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Salas RD; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Cassini MF; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Buttar C; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Wang W; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Farooq MS; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Shadaloey SAA; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Werba G; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Fnu A; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Yang F; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Hirsch C; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Glinski J; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Panjwani A; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Weitzner Y; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Cohen D; Department of Medicine, New York University School of Medicine, New York, NY, USA.
  • Asghar U; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA.
  • Miller G; S.A. Localio Laboratory, Departments of Surgery, New York University School of Medicine, New York, NY, USA. gedalyamil@gmail.com.
Oncogene ; 41(38): 4349-4360, 2022 09.
Article in En | MEDLINE | ID: mdl-35948648
Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment. Compared to primary tumor, liver metastases in both mice and humans are infiltrated by highly anergic T cells and MHCIIloIL10+ macrophages that are unable to present tumor-antigen. Moreover, a distinctive population of CD24+CD44-CD40- B cells dominate liver metastases. These B cells are recruited to the metastatic milieu by Muc1hiIL18hi tumor cells, which are enriched >10-fold in liver metastases. Recruited B cells drive macrophage-mediated adaptive immune-tolerance via CD200 and BTLA. Depleting B cells or targeting CD200/BTLA enhanced macrophage and T-cell immunogenicity and enabled immunotherapeutic efficacy of liver metastases. Our data detail the mechanistic underpinnings for compartment-specific immunotherapy-responsiveness and suggest that primary PDA models are poor surrogates for evaluating immunity in advanced disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Liver Neoplasms Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Oncogene Journal subject: BIOLOGIA MOLECULAR / NEOPLASIAS Year: 2022 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Liver Neoplasms Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Oncogene Journal subject: BIOLOGIA MOLECULAR / NEOPLASIAS Year: 2022 Type: Article Affiliation country: United States