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ResearchIn-Press PreviewGastroenterologyImmunologyOncology Open Access | 10.1172/jci.insight.198489

Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer

Jeremy B. Foote,1 Sujith Sarvesh,2 Sameer Al Diffalha,3 David K. Crossman,4 Changde Cheng,2 Myng-Hee Kim,1 Cherlene Hardy,1 Julienne L. Carstens,2 Kyoko Kojima,1 Bart J. Rose,5 and Christopher A. Klug1

1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Carstens, J. in: PubMed | Google Scholar

1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Rose, B. in: PubMed | Google Scholar

1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States of America

2Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, United States of America

3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States of America

4Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States of America

5Department of Surgery, The University of Alabama at Birmingham, Birmingham, United States of America

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Published May 11, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198489.
Copyright © 2026, Foote et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 11, 2026 - Version history
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Abstract

Antibody production by B cells has emerged as an important factor in regulating anti-tumor immunity with both suppressive and promotive roles in cancer. However, the specific impact of antibody deficiency during development of pancreatic ductal adenocarcinoma (PDAC) has not been explored. To address this question, we crossed the well-established KPC mouse model to mice lacking all circulating immunoglobulin (Ig) due to genetic ablation of both Ig secretion and Ig class switching (KPC-μSAID mice). KPC-μSAID mice exhibited a two-fold acceleration in tumor formation, a two-fold reduction in median survival, and increased liver metastases versus KPC-WT control mice. Immunofluorescence analysis of pancreatic tissues from antibody-sufficient KC- and KPC-WT mice showed that IgG was predominantly localized within extracellular matrix (ECM). Furthermore, in both KC- and KPC-μSAID mice, ECM density and podoplanin+ cancer-associated fibroblasts (CAFs) were significantly reduced. In the KPC-μSAID tumor microenvironment (TME), intratumoral myeloid-derived suppressor cells (MDSC) were also increased, while CD4+ and CD8+ T cells decreased, relative to tumor-bearing KPC-WT mice, with macrophage exhibiting a mixed polarization phenotype. These findings were recapitulated in antibody-subclass-deficient, KPC-AID mice, suggesting a potentially novel function of IgG in suppressing PDAC progression, by directly or indirectly regulating pancreatic fibrosis and the density of the ECM.

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Version history
  • Version 1 (May 11, 2026): In-Press Preview
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