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Case Reports
. 2021 Feb 5:5:PO.20.00287.
doi: 10.1200/PO.20.00287. eCollection 2021.

Tumor-Infiltrating Leukocyte Phenotypes Distinguish Outcomes in Related Patients With Pancreatic Adenocarcinoma

Jason M Link  1   2 , Shannon M Liudahl  3 , Courtney B Betts  3 , Shamilene Sivagnanam  4 , Kenna R Leis  4 , Mary McDonnell  2   5 , Carl R Pelz  2   4 , Brett Johnson  5 , Kelly J Hamman  1 , Dove Keith  2 , Jone E Sampson  1 , Terry K Morgan  3   6   7 , Charles D Lopez  2   8   7 , Lisa M Coussens  2   3   7 , Rosalie C Sears  1   2   7
Affiliations
Case Reports

Tumor-Infiltrating Leukocyte Phenotypes Distinguish Outcomes in Related Patients With Pancreatic Adenocarcinoma

Jason M Link et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/cci/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Carl R. PelzConsulting or Advisory Role, Immediate Family Member: NovartisCharles D. LopezConsulting or Advisory Role: Boston Scientific, Celgene, Boston Biomedical, Pfizer, Exelixis, Astellas Pharma Research Funding: Taiho Pharmaceutical Travel, Accommodations, Expenses: RenovoRxLisa M. CoussensEmployment: Oregon Health & Science University (OHSU) Honoraria: Prospect Creek Foundation, Lustgarten Foundation for Pancreatic Cancer Research, Syndax Pharmaceuticals, Inc: External Advisory Board, Carisma Therapeutics Inc: Scientific Advisory Board, Verseau Therapeutics, Inc, Scientific Advisory Board, Zymeworks, Inc, Scientific Advisory Board, CytomX Therapeutics, Inc, Kineta Inc, (P30) Koch Institute for Integrated Cancer Research, Massachusetts Inst. of Tech, (P30) Salk Institute Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Dana Farber Cancer Center Breast SPORE, (P30) Dana Farber/Harvard Cancer Center, (P30) University of California, San Diego Moores Cancer Center, Starr Cancer Consortium, Lustgarten Foundation for Pancreatic Cancer Research, Therapeutics Working Group, NIH/NCI-Frederick National Laboratory Advisory Committee (FNLAC), Susan G Komen Foundation, Komen Scholar Consulting or Advisory Role: Cell Signaling Technologies, Pharmacyclics, CytomX Therapeutics, Syndax, Carisma Therapeutics, Verseau Therapeutics, Zymeworks, Kineta, Inc, Abbvie, Shasqi Inc Research Funding: Syndax Pharmaceuticals Inc, Pharmacyclics, Cell Signaling Technologies, Innate Pharma, Deciphera Travel, Accommodations, Expenses: Cell Signaling Technologies, AstraZeneca, Pharmacyclics, Verseau, Carisma Therapeutics, CytomX Therapeutics, Zymeworks Other Relationship: Prospect Creek Foundation, Lustgarten Foundation for Pancreatic Cancer Research, (P30) Koch Institute for Integrated Cancer Research, Massachusetts Inst. of Tech. (2012-present; honorarium), (P30) Salk Institute Cancer Center: (2016-2020; honorarium), Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: (2016-present; honorarium), Dana Farber Cancer Center Breast SPORE: (2017-present; honorarium), (P30) Dana Farber/Harvard Cancer Center: (2019-present; honorarium), (P30) University of California, San Diego Moores Cancer Center (2019-present; honorarium), Cancer Research Institute (CRI): (2013-present; unpaid), The V Foundation for Cancer Research): (2013-present; unpaid), Starr Cancer Consortium: (2011-present, honorarium), Lustgarten Foundation for Pancreatic Cancer Research, Therapeutics Working Group: (2019-present; paid), NIH/NCI-Frederick National Laboratory Advisory Committee (FNLAC): (2016-present; daily honorarium), Susan G Komen Foundation, Komen Scholar (2020 – 2023; honorarium)Rosalie C. SearsConsulting or Advisory Role: Novartis No other potential conflicts of interest were reported

Figures

FIG 1.
FIG 1.
Disease courses for patients 1 (top) and 2 (bottom) aligned by date of diagnosis. The date when metastatic disease was first radiographically evident is indicated with an M in blue. CA19-9 test results are not shown because—for both patients—they were reproducibly approximately 90% lower than the 37 U/mL threshold for normal, even when the primary tumor was present. This result suggests a false negative result because of a Lewisa-b- antigen phenotype, as is the case for 5%-10% of Caucasian patients with PDAC.
FIG 2.
FIG 2.
PDAC subtype assignment based on histology and gene expression. (A) H&E stained sections and immunohistofluorescence for KRT5 (blue) and DAPI (white) from primary tumors. Regions of ductal or squamoid histology are indicated by black or blue arrows, respectively. Each scale bar is 0.5 mm. (B) H&E stained sections of metastases from Pt1 (lung) and Pt2 (ureter). Each scale bar is 0.5 mm. (C) PDAC subtyping of each patient's primary and metastatic tumors. Left panel: Spearman correlation coefficients for tumors from Pt1 and Pt2 compared with the published rank order of PDAssigner genes for classical (y-axis) and quasimesenchymal (x-axis) tumors. Right panel: scores from PurIST subtyping for each tumor. PDAC, pancreatic ductal adenocarcinoma.
FIG 3.
FIG 3.
(A) Mean cell density per ROI for mutually exclusive populations of Ki67+ tumor or epithelial cells, Ki67neg tumor or epithelial cells, fibroblasts, and leukocytes. (B) Mean cell density per ROI of selected leukocyte types. (C) Mean cell density per ROI of mutually exclusive CD4+ T cell subsets. (D) Densities of CD8+GRZB+ and CD8+Ki67+ T cells. (E) Relative densities of Th1-like macrophages to Th2-like macrophages and CD8+ T cells to granulocytes. For D and E, each dot represents one ROI and column heights represent the mean of ROIs. All statistical comparisons between each of the three tumors for all cell types were tested by Kruskal-Wallis one-way ANOVA. Only P values < 0.05 are given. ANOVA, analysis of variance; ROI, region of interest.
FIG 4.
FIG 4.
(A) Correlation between the densities of CD8+ T cells and granulocytes. Each dot represents one ROI. R2 and P values are based on a simple linear regression. (B) Granulocytes (CD66b+), tumor cells (PanKRT+), and fibroblasts (ACTA2+) in primary tumors from each patient. Scale bars represent 250 μm. ROI, region of interest.
FIG A1.
FIG A1.
(A) KRT (magenta) and CD45 (teal) expression and selected ROIs (yellow rectangles) used for mIHC analyses of tumors (scale bars represent 5 mm). Examples of tertiary lymph structures (TLSs) are indicated with white arrows. ROIs, regions of interest.
FIG A2.
FIG A2.
(A) Representative images of lymphocytes within TLSs. Scale bars represent 250 μm. (B) Mean number of B cells, CD4+ T cells, and CD8+ T cells within ROIs containing TLSs. P values are derived from a 2-tailed t test. ROIs, regions of interest; TLS, tertiary lymph structure.
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References

    1. Hidalgo M, Cascinu S, Kleeff J, et al. Addressing the challenges of pancreatic cancer: Future directions for improving outcomes Pancreatology 158–182015 - PubMed
    1. Cancer Facts & Figures 2018. American Cancer Society; 2018. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts...
    1. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer N Engl J Med 3792395–24062018 - PubMed
    1. Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer J Clin Oncol 271806–18132009 - PMC - PubMed
    1. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer Nature 4671114–11172010 - PMC - PubMed

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