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134 B and myeloid cell populations dominate in the metastasis compared to primary tumors of patients with pancreatic cancer
  1. Emily Greene1,
  2. Deon Doxie1,
  3. Maria Diab1,
  4. Bassel El-Rayes2,
  5. Shishir Maithel1,
  6. Juan Sarmiento1,
  7. Olatunji Alese1,
  8. Jayden Kim1,
  9. Cameron Herting3,
  10. Kavita Dhodapkar1,
  11. Madhav Dhodapkar1,
  12. Haydn Kissick1,
  13. Chrystal Paulos1 and
  14. Gregory Lesinski1
  1. 1Emory University, Atlanta, GA, USA
  2. 2University of Alabama at Birmingham, Birmingham, AL, USA
  3. 3Eli Lilly, Decatur, GA, USA


Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with 5-year survival rate of only 11% for patients. To date, nominal data on the immune profile within metastatic PDAC of patients exists. Since most patients present with late-stage disease, defining the immunological landscape of metastatic disease could inform next-generation immunotherapy for PDAC patients.

Methods Using a 37-marker mass cytometry panel, freshly digested tumor tissue from surgically resected primary (n=6) and untreated liver punch biopsy metastatic (n=10) PDAC samples were evaluated for various immune features at the single cell level. Stained samples were fixed, run on a Helios™ mass cytometer and analyzed via FlowJo and Cytobank software.

Results Fewer CD45+ cells were present in metastatic compared to primary PDAC tumors. CD19+ B Cells (3.65% ± 5.19 of live cells) dominated among other immune populations in metastases. Yet these B cells appeared less activated in metastatic PDAC, signified by fewer B cells expressing HLA-DR+ (57.67% ± 26.49 of CD19+) versus the primary cohort (84.95% ± 21.19 of CD19+). Primary samples had significantly more myeloid, NK and T cells (p=0.017, p<0.01 and p=0.015, respectively) versus metastases. Moreover, primary tumors had significantly higher CD38+CD4+ and CD38+CD8+ T cells (consistent with an exhausted phenotype), while ICOS and TIGIT were elevated on T reg from primary vs. metastatic tumors. A survey of checkpoints revealed that LAG-3, TIGIT, and PD-1 were the most prevalent markers across both CD4+ and CD8+ T cells. Further analysis revealed proliferative (Ki67+) CD11b+ cells at both tumor sites. Metastatic sites had prevalent PMN-MDSC-like myeloid cells, but few M-MDSC-like myeloid cells. In-depth analysis of T cell populations revealed more CD4+Tbet+ Th1-like cells in primary (37.83% ± 34.13 of CD4+) as compared to metastatic samples (12.34% ± 31.43 of CD4+). Antigen-exposed CD45RO+PD-1+ T cells (CD4+: 60% ± 33.28; CD8+: 44.17% ± 23.38) and TCF-1+PD-1+CD8+T cells (37.88% ± 33.27 of CD8+) were also predominant in primary samples.

Conclusions These data indicate for the first time that metastatic PDAC is dominated by B and myeloid cells. While T cells were more evident in primary tumors, these cells harbored phenotypic properties of exhaustion. This work lays the foundation for a detailed spatial investigation into primary and metastatic PDAC tumors and could identify actionable targets to improve immunotherapy for PDAC patients.

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