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

Link, Jason M.; Liudahl, Shannon M.; Betts, Courtney B.; Sivagnanam, Shamilene; Leis, Kenna R.; McDonnell, Mary; Pelz, Carl; Johnson, Brett; Hamman, Kelly Jo; Keith, Douglas S.; Sampson, Jone E.; Morgan, Terry K.; Lopez, Charles D.; Coussens, Lisa M.; Sears, Rosalie C.

doi:10.1200/po.20.00287

Cited by 2 publications

(2 citation statements)

References 64 publications

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“…Image processing, alignment of selected regions, and extraction of AEC signals was performed in MATLAB (V9.90.1592791) using the SURF algorithm in the Computer Vision Toolbox (The MathWorks, Inc) and FIJI as reported 55,119 . Pipeline for image processing and cell quantification was performed using FIJI (FIJI v 2.1), CellProfiler Version 4.1.3, and FCS Express Image Cytometry RUO (7.06.0015, De Novo Software, Glendale, CA) 120 . ER staining (ER, Novocastra, NCL-L-ER-6F11, 1:200, 1Hr) and pathological assessment for the intensity and % positive tumor cells for assigning an overall percent positive staining was done by a pathologist.…”

Section: Methodsmentioning

confidence: 99%

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

et al. 2021

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Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

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Section: Methodsmentioning

confidence: 99%

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

et al. 2021

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“…Of the ~20% of patients eligible for potentially curative resection of the primary tumor, only 30-35% survive >5 years. However, a subset of PDAC patients (~10%) who develop lung metastases survive significantly longer than patients with metastatic spread to other sites [14][15][16][17] ; in some cases, these patients survive >5 years with untreated, indolent lung metastases 18 . Patients with lung-restricted metastatic PDAC typically have slowly progressing disease, and may benefit from a metastatectomy 19 .…”

Section: Introductionmentioning

confidence: 99%

Ongoing Replication Stress Response and New Clonal T Cell Development Discriminate Between Liver and Lung Recurrence Sites and Patient Outcomes in Pancreatic Ductal Adenocarcinoma

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Pelz

Worth

et al. 2022

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Background and AimsMetastatic pancreatic adenocarcinoma (mPDAC) is lethal, yet a subset of patients who have metastatic disease that spreads only to the lung have better outcomes. We identified unique transcriptomic and immune features that distinguish patients who develop metastases in the liver (liver cohort) versus those with lung-avid but liver-averse mPDAC (lung cohort).MethodsWe used clinical data from the Oregon Pancreas Tissue Registry to identify PDAC patients with liver and/or lung metastases. Gene expression and genomic alteration data from 290 PDAC tumors were used to identify features unique to patients from the liver and lung cohorts. In parallel, T cell receptor sequencing data from 289 patients were used to identify immune features unique to patients in the lung cohort.ResultsLung cohort patients had better survival outcomes than liver cohort patients. Primary tumors from patients in the liver cohort expressed a novel gene signature associated with ongoing replication stress (RS) response predictive of poor patient outcome independent from known subtypes. In contrast, patients with tumors lacking the RS response signature survived longer, especially if their tumors had alterations in DNA damage repair genes. A subset of patients in the lung cohort demonstrated new T cell clonal development in their primary and metastatic tumors leading to diverse peripheral blood TCR repertoires.ConclusionLiver-avid metastatic PDAC is associated with an ongoing RS response, whereas tumors lacking the RS response with ongoing T cell clonal responses may have unique vulnerabilities allowing long-term survival in patients with lung-avid, liver-averse metastatic PDAC.

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

Cited by 2 publications

References 64 publications

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Ongoing Replication Stress Response and New Clonal T Cell Development Discriminate Between Liver and Lung Recurrence Sites and Patient Outcomes in Pancreatic Ductal Adenocarcinoma

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