Publications
Our researchers work diligently to not only make clinical advancements, but also scientific discoveries that are frequently published in the top scientific journals such as Nature and Cancer Discovery. Listed here are a selection of the most relevant articles authored by PCRC researchers.

Feature Articles
The PCRC was featured in a video from Let’s Win! Pancreatic Cancer. View the video here.
PCRC Researchers have been featured in two articles in Let's Win! Pancreatic Cancer. Most recently, PCRC Oncologist Dr. Kim Reiss-Binder for her work on PARP inhibitors, and PCRC Director Dr. Ben Z. Stanger for his work on "hot" and "cold" tumors.
The laboratories of Erica Carpenter and David Issadore have been developing new ways of extracting molecular information about pancreatic tumors from the blood:
- Ko J, Bhagwat N, Black T, Yee SS, Na YJ, Fisher SA, Kim J, Carpenter EL, Stanger BZ, Issadore D. miRNA profiling of magnetic nanopore-isolated extracellular vesicles for the diagnosis of pancreatic cancer. Cancer Res. 2018 Jul 1;78(13):3688-3697.
- Bhagwat N, Dulmage K, Pletcher CH Jr., Wang L, DeMuth W, Sen M, Balli D, Yee SS, Sa S, Tong F, Yu L, Moore JS, Stanger BZ, Dixon EP, Carpenter EL. An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters. Sci Rep. 2018 Mar; 8(1):5035.
Work from the laboratories of Anil Rustgi and Ben Stanger shows how tumor plasticity (the ability of tumor cells to adopt new features) influences metastasis in pancreatic cancer:
- Reichert M, Bakir B, Moreira L, Pitarresi JR, Feldmann K, Simon L, Suzuki K, Maddipati R, Rhim AD, Schlitter AM, Kriegsmann M, Weichert W, Wirth M, Schuck K, Schneider G, Saur D, Reynolds AB, Klein-Szanto AJ, Pehlivanoglu B, Memis B, Adsay NV, Rustgi AK. Regulation of Epithelial Plasticity Determines Metastatic Organotropism in Pancreatic Cancer. Dev Cell 2018 Jun 18;45(6):696-711.
- Aiello NM, Maddipati R, Norgard RJ, Balli D, Li J, Yuan S, Yamazoe T, Black T, Sahmoud A, Furth EE, Bar-Sagi D, Stanger BZ. EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration. Dev Cell 2018 Jun 18;45(6):681-695.
- (Highlighted in Developmental Cell): Lo HC, Zhang XH. EMT in Metastasis: Finding the Right Balance. Dev Cell 2018 Jun 18;45(6):663-665.
Work from the laboratories of Robert Vonderheide and Ben Stanger probes the molecular wiring of tumors that renders them sensitive or resistant to immune therapies (Penn Press Release):
- Li J, Byrne KT, Yan F, Yamazoe T, Chen Z, Baslan T, Richman LP, Lin JH, Sun YH, Rech AJ, Balli D, Hay CA, Sela Y, Merrell AJ, Liudahl SM, Gordon N, Norgard RJ, Yuan S, Yu S, Chao T, Ye S, Eisinger-Mathason TSK, Faryabi RB, Tobias JW, Lowe SW, Coussens LM, Wherry EJ, Vonderheide RH, Stanger BZ. Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy. Immunity 2018 Jul 17;49(1):178-193.
2021
- Norgard RJ, Stanger BZ. Isolation and Identification of EMT Subtypes. Methods Mol Biol. 2021;2179:315-326.
- Roehle K, Qiang L, Ventre KS, Heid D, Ali LR, Lenehan P, Heckler M, Crowley SJ, Stump CT, Ro G, Godicelj A, Bhuiyan AM, Yang A, Quiles Del Rey M, Biary T, Luoma AM, Bruck PT, Tegethoff JF, Nopper SL, Li J, Byrne PT, Pelletier M, Wucherpfennig KW, Stanger BZ, Akin JJ, Mancias JD, Agudo J, Dougan M, Dougan SK. cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes. Sci Transl Med. 2021 May 19;13(594):eabf5058.
- Reiss KA, Mick R, O'Hara MH, Teitelbaum U, Karasic TB, Schneider C, Cowden S, Southwell T, Romeo J, Izgur N, Hannan ZM, Tondon R, Nathanson KL, Vonderheide RH, Wattenberg MM, Beatty G, Domchek SM. Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021 May 10. (Online ahead of print.)
- Reiss KA, Vonderheide RH. Alternatives to Perpetual Chemotherapy for Metastatic Pancreatic Cancer. Clin Cancer Res. 2021 Apr 23. (Online ahead of print.)
- Liudahl SM, Betts CB, Sivagnanam S, Morales-Oyarvide V, da Silva A, Yuan C, Hwang S, Grossblatt-Wait A, Leis KR, Larson W, Lavoie MB, Robinson P, Dias Costa A, Vayryen SA, Clancy TE, Rubinson DA, Link J, Keith D, Horton W, Tempero MA, Vonderheide RH, Jaffee EM, Sheppard B, Goecks J, Sears RC, Park BS, Mori M, Nowak JA, Wolphin BM, Coussens LM. Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome. Cancer Discov. 2021 Mar 16;candisc. (Online ahead of print.)
- Li J, Yuan S, Norgard RJ, Yan F, Sun YH, Kim I, Merrell AJ, Sela Y, Jiang Y, Bhanu NV, Garcia BA, Vonderheide, Blanco A, Stanger BZ. Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer. Cancer Discov. 2021 Mar;11(3):736-753.
- Wattenberg MM, Herrera VM, Giannone MA, Gladney WL, Carpenter EL, Beatty GL. Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients. JCI Insight. 2021 Mar 8;6(5):e145389.
- Sela Y, Li J, Kuri P, Merrell AJ, Li N, Lengner C, Rompolas P, Stanger BZ. Dissecting phenotypic transitions in metastatic disease via photoconversion-based isolation. Elife. 2021 Feb 23;10:e63270.
- Pitarresi JR, Norgard RJ, Chiarella AM, Suzuki K, Bakir B, Sahu V, Li J, Zhao J, Marchand B, Wengyn MD, Hsieh A, Kim I, Zhang A, Sellin K, Lee V, Takano S, Miyahara Y, Ohtsuka M, Maitra A, Notta F, Kremer, Stanger BZ, Rustgi AK. PTHrP drives pancreatic cancer growth and metastasis and reveals a new therapeutic vulnerability. Cancer Discov. 2021 Feb 15;candisc.1098.2020. (Online ahead of print.)
- O'Hara MH, O'Reilly EM, Varadhachary G, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Mick R, Gherardini PF, Kitch LJ, Xu J, Samuel T, Karakunnel J, Fairchild J, Bucktrout S, LaVallee TM, Selinsky C, Chen RO, Trifan OC, Dugan U, Horak C, Hubbard-Lucey VM, Wherry EJ, Ibrahim R, Vonderheide RH. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021 Jan;22(1):118-131.
- Hannan Z, Yu S, Domchek S, Mamtani R, Reiss KA. Clinical Characteristics of Patients With Pancreatic Cancer and Pathogenic ATM Alterations. JNCI Cancer Spectr. 2021 Jan 23;5(2):pkaa121.
- Kahn BM, Lucas A, Alur RG, Wengyn MD, Schwartz GW, Li J, Sun K, Maurer HC, Olive KP, Faryabi RB, Stanger BZ. The vascular landscape of human cancer. J Clin Invest. 2021 Jan 19;131(2):e136655.
2020
- Natale CA, Li J, Pitarresi JR, Norgard RJ, Dentchev T, Capell BC, Seykora JT, Stanger BZ, Ridky TW. Pharmacologic Activation of the G Protein-Coupled Estrogen Receptor Inhibits Pancreatic Ductal Adenocarcinoma. Cell Mol Gastroenterol Hepatol. 2020;10(4):868-880.e1.
- Bear AS, Vonderheide RH, O'Hara MH. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell. 2020 Dec 14;38(6):788-802.
- Brown WS, McDonald PC, Nemirovsky O, Awrey S, Chafe SC, Schaeffer DF, Li J, Renouf DJ, Stanger BZ, Dedhar S. Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancer. Cell Rep Med. 2020 Nov 17;1(8):100131.
- Vonderheide RH, Bear AS. Tumor-Derived Myeloid Cell Chemoattractants and T Cell Exclusion in Pancreatic Cancer. Front Immunol. 2020 Nov 10;11:605619.
- Ko AH, Jordan AC, Tooker E, Lacey SF, Chang RB, Li Y, Venook AP, Tempero M, Damon L, Fong L, O'Hara MH, Levine BL, Melenhorst JJ, Plesa G, June CH, Beatty GL. Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer. Mol Ther. 2020 Nov 4;28(11):2367-2378.
- Bange EM, Doucette A, Gabriel PE, Porterfield F, Harrigan JJ, Wang R, Wojcieszynski AP, Boursi B, Mooney BI, Reiss KA, Mamtani R. Opportunity Costs of Receiving Palliative Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. JCO Oncol Pract. 2020 Aug;16(8):e678-e687.
- Bechard ME, Smalling R, Hayashi A, Zhong Y, Word AE, Campbell SL, Tran AV, Weiss VL, Iacobuzio-Donahue C, Wellen KE, McDonald OG. Pancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin for metastasis. Nat Commun. 2020 Aug 13;11(1):4055.
- Lin JH, Huffman AP, Wattenberg MM, Walter DM, Carpenter EL, Feldser DM, Beatty GL, Furth EE, Vonderheide RH. Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis. J Exp Med. 2020 Aug 3;217(8):e20190673.
- Tsujikawa T, Crocenzi T, Durham JN, Sugar EA, Wu AA, Onners B, Nauroth JM, Anders RA, Fertig EJ, Laheru DA, Reiss K, Vonderheide RH, Ko AH, Tempero MA, Fisher GA, Considine M, Danilova L, Brockstedt DG, Coussens LM, Jaffee EM, Le DT. Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer. Clin Cancer Res. 2020 Jul 15;26(14):3578-3588.
- Yang Z, LaRiviere MJ, Ko J, Till JE, Christensen T, Yee SS, Black TA, Tien K, Lin A, Shen H, Bhagwat N, Herman D, Adallah A, O'Hara MH, Vollmer CM, Katona, Stanger BZ, Issadore D, Carpenter EL. A Multianalyte Panel Consisting of Extracellular Vesicle miRNAs and mRNAs, cfDNA, and CA19-9 Shows Utility for Diagnosis and Staging of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2020 Jul 1;26(13):3248-3258.
- Yuan S, Nathan R, Sanchez-Rivera FJ, Li J, Bhanu NV, Yamazoe T, Lin JH, Merrell AJ, Sela Y, Thomas SK, Jiang Y, Plesset JB, Miller EM, Shi J, Garcia BA, Lowe SW, Asangani IA, Stanger BZ. Global Regulation of the Histone Mark H3K36me2 Underlies Epithelial Plasticity and Metastatic Progression. Cancer Discov. 2020 Jun;10(6):854-871.
- Huffman AP, Lin JH, Kim SI, Byrne KT, Vonderheide RH. CCL5 mediates CD40-driven CD4+ T cell tumor infiltration and immunity. JCI Insight. 2020 May 21;5(10):e137263.
- Ruscetti M, Morris 4th JP, Mezzadra R, Russell J, Leibold J, Romesser PB, Simon J, Klick A, Ho Y, Fennen M, Li J, Norgard RJ, Wilkinson JE, Alonso-Curbelo D, Sridharan R, Heller DA, de Stanchina E, Stanger BZ, Sherr CJ, Lowe SW. Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer. Cell. 2020 Apr 16;181(2):424-441.e21.
- Morrison AH, Diamond MS, Hay CA, Byrne KT, Vonderheide RH. Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity. Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):8022-8031.
- Li J, Yuan S, Norgard RJ, Yan F, Yamazoe T, Blanco A, Stanger BZ. Tumor Cell-Intrinsic USP22 Suppresses Antitumor Immunity in Pancreatic Cancer. Cancer Immune Res. 2020 Mar;8(3):282-291.
- Thomas SK, Lee J, Beatty GL. Paracrine and cell autonomous signalling in pancreatic cancer progression and metastasis. EBioMedicine. 2020 Mar;53:102662.
- Barsky AR, Reddy VK, Plastaras JP, Ben-Josef E, Metz JM, Wojcieszynski AP. Proton beam re-irradiation for gastrointestinal malignancies: a systematic review. J Gastrointest Oncol. 2020 Feb;11(1):187-202.
- Wattenberg MM, Asch D, Yu S, O'Dwyer PJ, Domchek SM, Nathanson KL, Rosen MA, Beatty GL, Siegelman ES, Reiss KA. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer. 2020 Feb;122(3):333-339.
- Vonderheide RH. CD40 Agonist Antibodies in Cancer Immunotherapy. Annu Rev Med. 2020 Jan 27;71:47-58.
2019
- Xu J, Sai H, Li Y, Jordan AC, McGettigan SE, Chen J-H, Bedoya F, Fraietta JA, Gladney WL, Joseph Melenhorst J, Beatty GL. Peripheral Blood T-Cell Fitness Is Diminished in Patients With Pancreatic Carcinoma but Can Be Improved With Homeostatic Cytokines. Cell Mol Gastroenterol Hepatol. 2019;8(4):656-658.e6.
- Qu D, Weygant N, Yao J, Chandrakesan P, Berry WL, May R, Pitts K, Husain S, Lightfoot S, Li M, Wang TC, An G, Clendenin C, Stanger BZ, Houchen CW. Overexpression of DCLK1-AL Increases Tumor Cell Invasion, Drug Resistance, and KRAS Activation and Can Be Targeted to Inhibit Tumorigenesis in Pancreatic Cancer. J Oncol. 2019 Aug 5;2019:6402925.
- Newton AD, Predina JD, Shin MH, Frenzel-Sulyok LG, Vollmer CM, Drebin JA, Singhai S, Lee MK 4th. Intraoperative Near-infared Imaging Can Identify Neoplasms and Aid in Real-time Margin Assessment During Pancreatic Resection. Ann Surg 2019 Jul;270(1):12-20.
- Maggino L, Liu JB, Thompson VM, Pitt HA, Ko CY, Vollmer CM Jr. Assessing the influence of experience in pancreatic surgery: a risk-adjusted analysis using the American College of Surgeons NSQIP database. HPB (Oxford) 2019 Dec;21(12):1773-1783.
- Karasic TB, O'Hara MH, Loaiza-Bonilla A, Reiss KA, Teitelbaum UR, Borazanci E, De Jesus-Acosta A, Redlinger C, Burrell JA, Laheru DA, Von Hoff DD, Amaravadi RK, Drebin JA, O'Dwyer PJ. Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol 2019 Jul 1;5(7):993-998.
- McDonald PC, Chafe SC, Brown WS, Saberi S, Swayampakula M, Venkateswaran G, Nemirovsky O, Gillespie JA, Karasinska JM, Kalloger SE, Supuran CT, Schaeffer DF, Bashashati A, Shah SP, Topham JT, Yapp DT, Li J, Renouf DJ, Stanger BZ, Dedhar S. Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia. Gastroenterology 2019 Sep;157(3):823-837.
- Qu D, Weygant N, Yao J, Chandrakesan P, Berry WL, May R, Pitts K, Husain S, Lightfoot S, Li M, Wang TC, An G, Clendenin C, Stanger BZ, Houchen CW. Overexpression of DCLK1-AL Increases Tumor Cell Invasion, Drug Resistance, and KRAS Activation and Can Be Targeted to Inhibit Tumorigenesis in Pancreatic Cancer. J Oncol. 2019 Aug 5.
- Markosyan N, Li J, Sun YH, Richman LP, Lin JH, Yan Fangxue Y, Quinones L, Sela Y, Yamazoe T, Gordon N, Tobias JW, Byrne KT, Rech AJ, FitzGerald GA, Stanger BZ, Vonderheide RH. Tumor cell-intrinsic EPHA2 suppresses anti-tumor immunity by regulating PTGS2 (COX-2) J Clin Invest. 2019 Jun 4;129(9):3594-3609.
- Marchand B, Pitarresi JR, Reichert M, Suzuki K, Laczkó D, Rustgi AK. PRRX1 isoforms cooperate with FOXM1 to regulate the DNA damage response in pancreatic cancer cells. Oncogene 2019 May;38(22):4325-4339.
- Balachandran VP, Beatty GL, Dougan SK. Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities. Gastroenterology 2019 May;156(7):2056-2072.
- Bauman B, Mick R, Martinez E, Lawless TM, Zinck L, Sinclair P, Fuhrer M, O'Hara M, Schneider CJ, O'Dwyer P, Plastaras J, Teitelbaum U, Reiss KA. Efficacy of Oral Cryotherapy During Oxaliplatin Infusion in Preventing Oral Thermal Hyperalgesia: A Randomized Trial. J Natl Compr Canc Netw 2019 Apr 1:17(4):358-364.
- Lee JW, Stone ML, Porrett PM, Thomas SK, Komar CA, Li JH, Delman D, Graham K, Gladney WL, Hua X, Black TA, Chien AL, Majmundar KS, Thompson JC, Yee SS, O'Hara MH, Aggarwal C, Xin D, Shaked A, Gao M, Liu D, Borad MJ, Ramanathan RK, Carpenter EL, Ji A, de Beer MC, de Beer FC, Webb NR, Beatty GL. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature 2019 Mar;567(7747):249-252.
- Li J, Stanger BZ. The tumor as organizer model. Science 2019 Mar 8;363(6431):1038-1039.
- Liu M, O'Connor RS, Trefely S, Graham K, Snyder NW, Beatty GL. Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal. Nat Immunol 2019 Jan 21:20(3):265-275.
- Carrer A, Trefely S, Zhao S, Campbell S, Norgard RJ, Schultz KC, Sidoli S, Parris JLD, Affronti HC, Sivanand S, Egolf S, Sela Y, Trizzino M, Gardini A, Garcia BA, Snyder NW, Stanger BZ, Wellen K. Acetyl-CoA metabolism supports multi-step pancreatic tumorigenesis. Cancer Discov. 2019 Jan 9. pii: CD-18-0567. doi: 10.1158/2159-8290.CD-18-0567. [Epub ahead of print].
- Beatty GL, Shahda S, Beck T, Uppal N, Cohen SJ, Donehower R, Gabayan AE, Assad A, Switzky J, Zhen H, Von Hoff DD. A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Oncologist 2019 Jan;24(1):14-e10.
2018
- Maity A, Mick R, Huang AC, George SM, Farwell MD, Lukens JN, Berman AT, Mitchell TC, Bauml J, Schuchter LM, O'Hara M, Lin LL, Demichele A, Christodouleas JP, Haas NB, Patsch DM, Hahn SM, Minn AJ, Wherry EJ, Vonderheide RH. A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours. Br J Cancer 2018 Nov; 119(10):1200-1207.
- Karakasheva TA, Lin EW, Tang Q, Qiao E, Waldron TJ, Soni M, Klein-Szanto AJ, Sahu V, Basu D, Ohashi S, Baba K, Giaccone ZT, Walker SR, Frank DA, Wileyto EP, Long Q, Dunagin M, Raj A, Diehl JA, Wong KK, Bass AJ, Rustgi AK. IL-6 mediates cross-talk between activated fibroblasts and tumor cells in the tumor microenvironment. Cancer Res. 2018 Jul 5; 78(17):4957-4970.
- Ecker BL, McMillan MT, Maggino L, Vollmer CM Jr. Taking Theory to Practice: Quality Improvement for Pancreaticoduodenectomy and Development and Integration of the Fistula Risk Score. J. Am. Coll. Surg. 2018 Jul 5; 227(4):430-438.e1.
- Ko J, Bhagwat N, Black T, Yee SS, Na YJ, Fisher SA, Kim J, Carpenter EL, Stanger BZ, Issadore D. miRNA profiling of magnetic nanopore-isolated extracellular vesicles for the diagnosis of pancreatic cancer. Cancer Res. 2018 Jul 1;78(13):3688-3697.
- Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, Gladney WL, Levine BL, Melenhorst JJ, Plesa G, June CH. Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastasis in a Phase 1 Trial. Gastroenterology 2018 Jul;155(1):29-32.
- Lee KE, Spata M, Maduka R, Vonderheide RH, Simon MC. Hif1α Deletion Limits Tissue Regeneration via Aberrant B Cell Accumulation in Experimental Pancreatitis. Cell Rep. 2018 Jun 19;23(12):3457-3464.
- Reichert M, Bakir B, Moreira L, Pitarresi JR, Feldmann K, Simon L, Suzuki K, Maddipati R, Rhim AD, Schlitter AM, Kriegsmann M, Weichert W, Wirth M, Schuck K, Schneider G, Saur D, Reynolds AB, Klein-Szanto AJ, Pehlivanoglu B, Memis B, Adsay NV, Rustgi AK. Regulation of Epithelial Plasticity Determines Metastatic Organotropism in Pancreatic Cancer. Dev Cell 2018 Jun 18;45(6):696-711.
- Aiello NM, Maddipati R, Norgard RJ, Balli D, Li J, Yuan S, Yamazoe T, Black T, Sahmoud A, Furth EE, Bar-Sagi D, Stanger BZ. EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration. Dev Cell 2018 Jun 18;45(6):681-695.
- (Highlighted in Developmental Cell): Lo HC, Zhang XH. EMT in Metastasis: Finding the Right Balance. Dev Cell 2018 Jun 18;45(6):663-665.
- Morrison AH, Byrne KT, Vonderheide RH. Immunotherapy and Prevention of Pancreatic Cancer. Trends Cancer 2018 Jun;4(6):418-428.
- Abbruzzese JL, Andersen DK, Borrebaeck CAK, Chari ST, Costello E, Cruz-Monserrate Z, Eibl G, Engleman EG, Fisher WE, Habtezion A, Kim SK, Korc M, Logsdon C, Lyssiotis CA, Pandol SJ, Rustgi A, Wolfe BM, Zheng L, Powers AC. The Interface of Pancreatic Cancer With Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 2018 May/Jun;47(5):516-525. doi: 10.1097/MPA.0000000000001037.
- Rech AJ, Dada H, Kotzin JJ, Henao-Mejia J, Minn AJ, Twyman-Saint Victor C, Vonderheide RH. Radiotherapy and CD40 activation separately augment immunity to checkpoint blockade in cancer. Cancer Res. 2018 May 29; 78(15):4282-4291.
- Shroff RT, Hendifar A, McWilliams RR, Geva R, Epelbaum R, Rolfe L, Goble S, Lin KK, Biankin AV, Giordano H, Vonderheide RH, Domchek SM. Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation. JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.17.00316. Epub 2018 May 16.
- Tamura K, Yu J, Hata T, Suenaga M, Shindo K, Abe T, MacGregor-Das A, Borges M, Wolfgang CL, Weiss MJ, He J, Canto MI, Petersen GM, Gallinger S, Syngal S, Brand RE, Rustgi A, Olson SH, Stoffel E, Cote ML, Zogopoulos G, Potash JB, Goes FS, McCombie RW, Zandi PP, Pirooznia M, Kramer M, Parla J, Eshleman JR, Roberts NJ, Hruban RH, Klein AP, Goggins M. Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer. Proc. Natl. Acad. Sci. U.S.A. 2018 May 1;115(18):4767-4772.
- Maggino L, Liu JB, Ecker BL, Pitt HA, Vollmer CM Jr. Impact of Operative Time on Outcomes after Pancreatic Resection: A Risk-Adjusted Analysis Using the American College of Surgeons NSQIP Database. J. Am. Coll. Surg. 2018 May;226(5):844-857.
- Vonderheide RH. The Immune Revolution: A Case for Priming, Not Checkpoint. Cancer Cell 2018 Apr 9;33(4):563-569.
- Karakasheva TA, Dominguez GA, Hashimoto A, Lin EW, Chiu C, Sasser K, Lee JW, Beatty GL, Gabrilovich DI, Rustgi AK. CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients. JCI Insight 2018 Mar 22;3(6). pii:97022.
- Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, Gladney WL, Levine BL, Melenhorst JJ, Plesa G, June CH. Activity of Mesothelin-specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial. Gastroenterology 2018 Mar 20; 155(1):29-32.
- Bhagwat N, Dulmage K, Pletcher CH Jr., Wang L, DeMuth W, Sen M, Balli D, Yee SS, Sa S, Tong F, Yu L, Moore JS, Stanger BZ, Dixon EP, Carpenter EL. An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters. Sci Rep. 2018 Mar; 8(1):5035.
- Shabason JE, Chen J, Apisarnthanarax S, Damjanov N, Giantonio B, Loaiza-Bonilla A, O'Dwyer PJ, O'Hara M, Reiss KA, Teitelbaum U, Wissel P, Drebin JA, Vollmer C, Kochman M, Mick R, Vergara N, Jhala N, Doucette A, Lukens JN, Plastaras JP, Metz JM, Ben-Josef E. A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Cancer Chemother. Pharmacol. 2018 Mar; 81(3):609-614.
- Rech AJ, Balli D, Mantero A, Ishwaran H, Nathanson KL, Stanger BZ, Vonderheide RH. Tumor Immunity and Survival as a Function of Alternative Neopeptides in Human Cancer. Cancer Immunol. Res. 2018 Jan 16; doi: 10.1158/2326-6066.CIR-17-0559. [Epub ahead of print].
2017
- Long KB, Collier AI, Beatty GL. Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance. Mol Immunol. 2017 Dec 19. pii: S0161-5890(17)30596-5. doi: 10.1016/j.molimm.2017.12.003. [Epub ahead of print].
- Moreira L, Bakir B, Chatterji P, Dantes Z, Reichert M, Rustgi AK. Pancreas 3D Organoids: Current and Future Aspects as a Research Platform for Personalized Medicine in Pancreatic Cancer. Cell Mol. Gastroenterol. Hepatol. 2017 Dec 16;5(3):289-298.
- Bengsch F, Knoblock DM, Liu A, McAllister F, Beatty GL. CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer. Cancer Immunol. Immunother. 2017 Dec; 66(12):1609-1617.
- Ko J, Bhagwat N, Yee SS, Ortiz N, Sahmoud A, Black T, Aiello NM, McKenzie L. O'Hara M, Redlinger C, Romeo J, Carpenter EL, Stanger BZ, Issadore D. Combining Machine Learning and Nanofluidic Technology to Diagnose Pancreatic Cancer Using Exosomes. ACS Nano 2017 Nov 28;11(11):11182-11193.
- Lo A, Li CP, Buza EL, Blomberg R, Govindaraju P, Avery D, Monslow J, Hsiao M, Puré E. Fibroblast activation protein augments progression and metastasis of pancreatic ductal adenocarcinoma. JCI Insight 2017 Oct 5;2(19). pii: 92232.
- Ko J, Bhagwat N, Yee SS, Black T, Redlinger C, Romeo J, O'Hara M, Raj A, Carpenter EL, Stanger BZ, Issadore D. A magnetic micropore chip for rapid (<1 hour) unbiased circulating tumor cell isolation and in situ RNA analysis. Lab Chip 2017 Sep 12;17(18):3086-3096.
- Long KB, Tooker G, Tooker E, Luque SL, Lee JW, Pan X, Beatty GL. IL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma. Mol. Cancer Ther. 2017 Sep; 16(9):1898-1908.
- Boimel PJ, Berman AT, Li J, Apisarnthanarax S, Both S, Lelionis K, Larson GL, Teitelbaum U, Lukens JN, Ben-Josef E, Metz JM, Plastaras JP. Proton beam reirradiation for locally recurrent pancreatic adenocarcinoma. J. Gastrointest. Oncol. 2017 Aug;8(4):655-674.
- Kim J, Bamlet WR, Oberg AL, Chaffee KG, Donahue G, Cao XJ, Chari S, Garcia BA, Petersen GM, Zaret KS. Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers. Sci. Transl. Med. 2017 Jul 12;9(398). pii. eaah5583.
- Aiello NM, Brabletz T, Kang Y, Nieto MA, Weinberg RA, Stanger BZ. Upholding a role for EMT in pancreatic cancer metastasis. Nature 2017 Jul 5;547(7661):E7-E8.
- Balli D, Rech AJ, Stanger BZ, Vonderheide RH. Immune Cytolytic Stratifies Molecular Subsets of Human Pancreatic Cancer. Clin. Cancer Res. 2017 Jun 15;23(12):3129-3138.
- McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, Stauffer KM, Makohon-Moore A, Zhong Y, Wu H, Wellen KE, Locasale JW, Iacobuzio-Donahue CA, Feinberg AP. Epigenetic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat. Genet. 2017 Mar;49(3):367-376.
- Boursi B, Finkelman B, Giantonio BJ, Haynes K, Rustgi AK, Rhim AD, Mamtani R, Yang YX. A Clinical Prediction Model to Assess Risk for Pancreatic Cancer Among Patients With New-Onset Diabetes. Gastroenterology 2017 Mar; 152(4):840-850.e3.
- Rech AJ, Vonderheide RH. T-Cell Transfer Therapy Targeting Mutant KRAS. N. Engl. J. Med. 2017 Feb 16;376(7):e11.
- Zhang Y, Velez-Delgado A, Matthew E, Li D, Mendez FM, Flannagan K, Rhim AD, Simeone DM, Beatty GL, Pasca de Magliano M. Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut. 2017 Jan;66(1):124-136.
- Kalbasi A, Komar C, Tooker GM, Liu M, Lee JW, Gladney WL, Ben-Josef E, Beatty GL. Tumor-derived CCL2 mediates resistance to radiotherapy in Pancreatic Ductal Adenocarcinoma. Clin. Cancer Res. 2017 Jan 1;23(1):137-148.
2016
- Chao T, Furth EE, Vonderheide RH. CXCR2-Dependent Accumulation of Tumor-Associated Neutrophils Regulates T-Cell Immunity in Pancreatic Ductal Adenocarcinoma. Cancer Immunol. Res. 2016 Nov;4:(11):968-982.
- Beatty GL, O'Hara M. Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps. Pharmacol Ther. 2016 Oct;166:30-39.
- Aiello NM, Bajor DL, Norgard RJ, Sahmoud A, Bhagwat N, Pham MN, Cornish TC, Iacobuzio-Donahue CA, Vonderheide RH, Stanger BZ. Metastatic progression is associated with dynamic changes in the local microenvironment. Nat. Commun. 2016 Sep 15;7:12819.
- Evans RA, Diamond MS, Rech AJ, Chao T, Richardson MW, Lin JH, Bajor DL, Byrne KT, Stanger BZ, Riley JL, Markosyan N, Winograd R, Vonderheide RH. Lack of immunoediting in murine pancreatic cancer reversed with neoantigen. JCI Insight 2016 Sep 8;1(14). pii:e88328.
- Heeg S, Das KK, Reichert M, Bakir B, Takano S, Caspers J, Aiello NM, Wu K, Neesse A, Maitra A, Iacobuzio-Donahue CA, Hicks P, Rustgi AK. ETS-Transcription Factor ETV1 Regulates Stromal Expansion and Metastasis in Pancreatic Cancer. Gastroenterology 2016 Sep;151(3):540-553.e14.
- Byrne KT, Leisenring NH, Bajor DL, Vonderheide RH. CSF-1R-Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody is Given Before But Not After Chemotherapy. J. Immunol. 2016 Jul 1;197(1):179-187.
- Byrne KT, Vonderheide RH. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer. Cell Reports 2016 Jun 21;15(12):2719-2732.
- Winter JM, Jiang W, Basturk O, Mino-Kenudson M, Fong ZV, Tan WP, Lavu H, Vollmer CM, Furth EE, Haviland D, Klimstra DS, Jarnagin WR, Lillemoe KD, Yeo CJ, Fernandez-Del Castillo C, Allen PJ. Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (≤20-mm Invasive Component): A Multi-institutional Analysis. Ann. Surg. 2016 Apr; 263(4):793-801.
- Long KB, Gladney WL, Tooker GM, Graham K, Fraietta JA, Beatty GL. IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. Cancer Discovery 2016 Apr;6(4)400-413.
- Lee KE, Spata M, Bayne LJ, Buza EL, Durham AC, Allman D, Vonderheide RH, Simon MC. Hif1a Deletion Reveals Pro-Neoplastic Function of B Cells in Pancreatic Neoplasia. Cancer Discovery 2016 Mar;6(3):256-269.
- Takano S, Reichert M, Bakir B, Das KK, Nishida T, Miyazaki M, Heeg S, Collins MA, Marchand B, Hicks PD, Maitra A, Rustgi AK. Prrx1 isoform switching regulates pancreatic cancer invasion and metastatic colonization. Genes & Development 2016 Jan 15;30(2):233-247.
2015
- Maddipati R, Stanger BZ. Pancreatic Cancer Metastases Harbor Evidence of Polyclonality. Cancer Discovery 2015 Oct;5(10):1086-97.
- Beatty GL, Winograd R, Evans RA, Long KB, Luque SL, Lee JW, Clendenin C, Gladney WL, Knoblock DM, Guirnalda PD, Vonderheide RH. Exclusion of T Cells from Pancreatic Carcinomas in mice is regulated by Ly6C(low) F4/80(+) extratumoral macrophages. Gastroenterology 2015 Jul;149(1):201-10.
- Hoffman RL1, Gates JL2, Kochman ML3, Ginsberg GG3, Ahmad NA3, Chandrasekhara V3, Furth EE4, Vollmer CM2, Drebin JA. Analysis of cyst size and tumor markers in the management of pancreatic cysts: support for the original Sendai criteria. J. Am. Coll. Surg. 2015 Jun; 220(6):1087-95.
- Kim J, Zaret KS. Reprogramming of human cancer cells to pluripotency for models of cancer progression. EMBO J. 2015 Mar 12;34(6):739-47.
- Winograd R, Byrne KT, Evans RA, Odorizzi PM, Meyer AR, Bajor DL, Clendenin C, Stanger BZ, Furth EE, Wherry EJ, Vonderheide RH. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 Blockade and improves survival in Pancreatic Carcinoma. Cancer Immunol. Res. 2015 Apr;3(4):399-411.
- Aiello NM, Stanger BZ. Echoes of the embryo: Using the developmental biology toolkit to study cancer. Dis Model Mech. 2016 Feb 1;9(2):105-14.
Legends:
On the cover (Immunity): Tumors possess heterogeneous immune tumor microenvironments (TMEs), with some that are T-cell inflamed (hot) and others that are non-T-cell inflamed (cold). In this issue of Immunity, Li, Byrne et al. (178–193) generate an experimental system that recapitulates this heterogeneity in mouse models of pancreatic cancer. The authors find that tumor-intrinsic features determine the nature of the immune infiltrate and reveal a central role for the chemokine CXCL1 in the generation of a non-T-cell-inflamed tumor microenvironment. Cold tumors are depicted as blue water, wherein cancer cells (crab) recruit suppressive myeloid cells (yellow sea anemone) to protect against attack from T cells (octopus). In hot tumors (red water), cancer cells fail to recruit protective myeloid cells and are targeted by T cells following immunotherapy. Illustration by Cuncun Zhao.
On the cover (Developmental Cell): Tumor cells that have undergone epithelial-mesenchymal transition (EMT) and entered the circulation are represented by koi fish in a pond. Cells that undergo partial EMT (group of speckled fish) internalize their epithelial junctions (speckles) and disseminate by collective migration. In contrast, cells that undergo complete EMT (solitary fish) repress the epithelial program through transcriptional regulation and disseminate as single cells. For more on cancer cell migration modes, see Aiello et al. (pp.681–695) and the related paper from Reichert et al. (pp. 696–711).
On the cover (Cancer Cell): Fresh insights for exploiting the immune system's strengths and vulnerabilities are paving the way to a revolution in cancer treatment. Following FDA approvals of immune checkpoint antibodies and chimeric antigen receptor T cells, current research efforts now aim to understand the role of T cell priming and dysfunction in the tumor microenvironment as well as the influence of other immune regulatory factors, including the microbiome. Researchers are also investigating the effects of oncolytic viruses on anti-tumor immunity. The translation of these scientific advances to novel clinical trials is as rapid and as expansive as ever before, suggesting we have only seen the tip of the iceberg for cancer immunotherapy. For more details, see the four Perspective articles and one Review article in this issue. Artwork by Abby Ernst, Penn Medicine.
On the cover (Cancer Immunology Research): Patients respond better to immunotherapy if their tumors have generated abundant neopeptides. However, not all identified neopeptides are immunogenic, even after selection based on algorithms predicting affinity for class I or class II major histocompatibility antigens. By comparing the neopeptides from more than 6,300 patients with 27 types of tumors, Rech and colleagues identified alternatively defined neopeptides by their ability to bind to MHC at least 10 times better than their normal unmutated counterparts. These “ADNs” provide a rich, unexplored pool of possible antigenic targets for immunotherapy. Read more starting on page 276 of this issue. The original image of a Masson's trichrome stained pancreatic tumor was provided by Dr. Emma E. Furth, Professor of Pathology and Laboratory Medicine, Head of Gastrointestinal Pathology, Hospital of the University of Pennsylvania. Connective tissue, blue; cells, magenta. Artwork by Lewis Long.