Immunobiology and immunosurveillance in patients with intraductal papillary mucinous neoplasms (IPMNs), premalignant precursors of pancreatic adenocarcinomas.
Premalignant lesions for many cancers have been identified, and efforts are currently directed toward identification of antigens expressed on these lesions that would provide suitable targets for vaccines for cancer prevention. Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts of which a subset has the potential to progress to cancer. Currently, there are no validated predictive markers for progression to malignancy. We hypothesized that the presence or absence of immune surveillance of these lesions would be one such factor. Here we show that the tumor antigen MUC1, which is abnormally expressed on pancreatic cancer and is a target for cancer immunosurveillance, is also abnormally expressed on premalignant IPMN. We show that some IPMN patients make MUC1-specific IgG. Moreover, we show evidence of CD4 and CD8 T cell infiltration into IPMN areas of high dysplasia suggesting an ongoing immune response within the lesions. We also found, however, increased levels of circulating myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in some IPMN patients as well as evidence of T cell exhaustion. Further studies correlating immunosurveillance or immunosuppression with IPMN progression to malignancy will help define the immune response as a biomarker of risk, leading potentially to a vaccine to boost spontaneous immunity and prevent progression to cancer.
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, E1040 BST, Pittsburgh, PA, 15261, USA.
Pamela L
PL
Beatty
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, E1040 BST, Pittsburgh, PA, 15261, USA.
Rick
R
van der Geest
Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Jana G
JG
Hashash
Department of Regenerative Surgery, Fukushima Medical University, Fukushima, Japan.
Takashi
T
Kimura
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Dmitriy
D
Gutkin
Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Randall E
RE
Brand
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, E1040 BST, Pittsburgh, PA, 15261, USA. ojfinn@pitt.edu.
Olivera J
OJ
Finn
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000276:immunology* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods*; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood / Q000276:immunology / Q000473:pathology
D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1
CITIM 2015; Cancer vaccines; IPMN; Immunosurveillance; MUC1; Pancreatic cancer