Multimodal Mapping of the Immune Landscape in Human Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that has rendered it largely refractory to immunotherapy. We used single-cell RNA sequencing on patient tumors and matched blood, and we uncovered a previously unappreciated, complex environment of immune-suppressive cellular interactions. These experiments reveal immune checkpoint expression heterogeneity on individual patient T cells, with corresponding ligands on neoplastic and myeloid cells. TIGIT was upregulated on tumor infiltrating CD8+ T cells and was the only checkpoint receptor consistently expressed by exhausted CD8+ T cells. Clinical annotation of the samples revealed that the exhausted signature is most prominent in patients with advanced stages of disease. Our findings suggest individualized combination therapy, involving anti-TIGIT therapies, may be necessary to extend the benefits of immunotherapy to pancreatic cancer patients.

• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Cohort
• Total number of consented subjects: 25
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample
• MeSH
• Gene

Inclusion criteria:

1. Patient must be at least 18 years old.
2. Patients being seen or previously treated within the University of Michigan Health System and/or the Comprehensive Cancer Center.
3. Patient must be willing and able to provide written informed consent.

Exclusion criteria:

1. Doesn't meet inclusion criteria

• Primary Phenotype: Carcinoma, Pancreatic Ductal

• TIGIT

• Principal Investigator
  • Marina Pasca di Magliano, PhD. University of Michigan, Ann Arbor, MI, USA.
• Funding Sources
  • R01CA151588. National Institutes of Health, Bethesda, MD, USA.
  • R01CA198074. National Institutes of Health, Bethesda, MD, USA.
  • U01CA224145. National Institutes of Health, Bethesda, MD, USA.