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1. Figure S3 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Figure 3: Association of chemokine expression with a T cell-inflamed phenotype was validated in a second independent PDAC patient cohort

Published
2023
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2. Table S1 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Table 1: Top 99 genes associating with CD8+ TIL counts in primary resected cases

Published
2023
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3. Table S3 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Table 3: Summary statistics for cellularity in 4-chemokinehi and 4-chemokinelo groups in primary resections

Published
2023
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4. Figure S6 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Figure 6: Immune phenotypes were not impacted by cellularity in metastases

Published
2023
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5. Table S2 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Table 2: Top 100 upregulated genes in 4-chemokinehi and 4-chemokinelo patients

Published
2023
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6. Data from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Purpose:The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC.Experimental Design:Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from The Cancer Genome Atlas and 92 PDACs from the Australian International Cancer Genome Consortium. We explored associations between immune cell counts by immunohistochemistry, chemokine expression, and transcriptional hallmarks of antitumor immunity by RNA sequencing (RNA-seq), and mutational burden by whole-genome sequencing.Results:Among all known human chemokines, a coregulated set of four (CCL4, CCL5, CXCL9, and CXCL10) was strongly associated with CD8+ T-cell infiltration (P < 0.001). Expression of this “4-chemokine signature” positively correlated with transcriptional metrics of T-cell activation (ZAP70, ITK, and IL2RB), cytolytic activity (GZMA and PRF1), and immunosuppression (PDL1, PD1, CTLA4, TIM3, TIGIT, LAG3, FASLG, and IDO1). Furthermore, the 4-chemokine signature marked tumors with increased T-cell activation scores (MHC I presentation, T-cell/APC costimulation) and elevated expression of innate immune sensing pathways involved in T-cell priming (STING and NLRP3 inflammasome pathways, BATF3-driven dendritic cells). Importantly, expression of this 4-chemokine signature was consistently indicative of a T-cell–inflamed phenotype across primary PDAC and PDAC liver metastases.Conclusions:A conserved 4-chemokine signature marks resectable and metastatic PDAC tumors with an active antitumor phenotype. This could have implications for the appropriate selection of PDAC patients in immunotherapy trials.

Published
2023
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7. Table S4 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Table 4: Summary statistics for cellularity between 4-chemokinehi and 4-chemokinelo groups in liver metastases

Published
2023
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8. Figure S5 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Figure 5: The 4-chemokine signature identified an antitumor phenotype in liver metastases, independent of mutational burden

Published
2023
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9. Figure S2 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Figure 2: Transcriptomic subtypes versus 4-chemokinehi and 4-chemokinelo in both primary and metastatic tumours

Published
2023
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10. Figure S1 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Steven Gallinger, George Zogopoulos, Yifan Wang, Ashton Connor, Jennifer J. Knox, Julie M. Wilson, Grainne M. O'Kane, Susan J. Done, Pamela S. Ohashi, Faiyaz Notta, Tracy L. McGaha, Rama Khokha, Peter Bronsert, Foram Vyas, Dianne Chadwick, Sheng-Ben Liang, Sharon Dhaliwal, Niandong Li, Jing Xu, John M.S. Bartlett, Angela De Luca, Ilinca M. Lungu, Robert E. Denroche, Amy Zhang, Sandra E. Fischer, Mehdi Masoomian, Aaditeya Jhaveri, Prashant P. Bavi, Gun-Ho Jang, Barbara Grünwald, and Joan M. Romero

Abstract

Supplementary Figure 1: Overview of methodology and cohorts

Published
2023
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12. A Four-Chemokine Signature Is Associated with a T-cell-Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Author

Robert E. Denroche, Rama Khokha, Sheng-Ben Liang, Dianne Chadwick, Gun-Ho Jang, Angela De Luca, Peter Bronsert, Sharon Dhaliwal, Barbara Grünwald, John M. S. Bartlett, Prashant Bavi, Aaditeya Jhaveri, Susan J. Done, Jennifer J. Knox, George Zogopoulos, Amy Zhang, Ilinca Lungu, Tracy L. McGaha, Joan Miguel Romero, Foram Vyas, Ashton A. Connor, Steven Gallinger, Sandra Fischer, Grainne M. O'Kane, Julie M. Wilson, Pamela S. Ohashi, Yifan Wang, Faiyaz Notta, Niandong Li, Jing Xu, and Mehdi Masoomian

Subjects
0301 basic medicine, Cancer Research, Chemokine, endocrine system diseases, T cell, medicine.medical_treatment, CD8-Positive T-Lymphocytes, Chemokine CXCL9, CCL5, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Immune system, Databases, Genetic, medicine, Biomarkers, Tumor, CXCL10, Humans, RNA-Seq, Chemokine CCL4, Chemokine CCL5, biology, business.industry, Liver Neoplasms, Computational Biology, Immunotherapy, Immune Checkpoint Proteins, Phenotype, digestive system diseases, 3. Good health, Chemokine CXCL10, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Mutation, biology.protein, Cancer research, CXCL9, business
Abstract

Purpose: The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC. Experimental Design: Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from The Cancer Genome Atlas and 92 PDACs from the Australian International Cancer Genome Consortium. We explored associations between immune cell counts by immunohistochemistry, chemokine expression, and transcriptional hallmarks of antitumor immunity by RNA sequencing (RNA-seq), and mutational burden by whole-genome sequencing. Results: Among all known human chemokines, a coregulated set of four (CCL4, CCL5, CXCL9, and CXCL10) was strongly associated with CD8+ T-cell infiltration (P < 0.001). Expression of this “4-chemokine signature” positively correlated with transcriptional metrics of T-cell activation (ZAP70, ITK, and IL2RB), cytolytic activity (GZMA and PRF1), and immunosuppression (PDL1, PD1, CTLA4, TIM3, TIGIT, LAG3, FASLG, and IDO1). Furthermore, the 4-chemokine signature marked tumors with increased T-cell activation scores (MHC I presentation, T-cell/APC costimulation) and elevated expression of innate immune sensing pathways involved in T-cell priming (STING and NLRP3 inflammasome pathways, BATF3-driven dendritic cells). Importantly, expression of this 4-chemokine signature was consistently indicative of a T-cell–inflamed phenotype across primary PDAC and PDAC liver metastases. Conclusions: A conserved 4-chemokine signature marks resectable and metastatic PDAC tumors with an active antitumor phenotype. This could have implications for the appropriate selection of PDAC patients in immunotherapy trials.

Published
2019

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