Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

被引：44

作者：

Torphy, Robert J. ^{[1
]}

Schulick, Richard D. ^{[1
]}

Zhu, Yuwen ^{[1
]}

机构：

[1] Univ Colorado, Dept Surg, Div Surg Oncol, Anschutz Med Campus,Res 1 North,12800 E 19th Ave, Aurora, CO 80045 USA

来源：

MOLECULAR CARCINOGENESIS | 2020年 / 59卷 / 07期

基金：

美国国家卫生研究院;

关键词：

desmoplasia; immunotherapy; pancreatic ductal adenocarcinoma; stroma; TERTIARY LYMPHOID STRUCTURES; T-CELLS; ANTITUMOR IMMUNITY; MACROPHAGES; STROMA; IDENTIFICATION; INFLAMMATION; ACTIVATION; INHIBITION; SURVIVAL;

D O I：

10.1002/mc.23179

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Immunotherapy has revolutionized cancer treatment for several hematologic and solid organ malignancies; however, pancreatic cancer remains unresponsive to conventional immunotherapies. Several characteristics of pancreatic cancer present challenges to successful treatment with immunotherapy, including its aggressive biology, poor immunogenicity, and abundant desmoplastic stroma which can impede effector T cell infiltration and promote an immunosuppressive microenvironment. In this review, we evaluate the current understanding of the immune and stromal landscapes of pancreatic cancer, discuss the successes and failures of stroma-targeted therapies, and highlight how stroma-directed therapies may be synergistic with immunotherapy.

引用

页码：775 / 782

页数：8

共 68 条

[1] Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma [J].

Amaria, Rodabe N. ;

Reddy, Sangeetha M. ;

Tawbi, Hussein A. ;

Davies, Michael A. ;

Ross, Merrick, I ;

Glitza, Isabella C. ;

Cormier, Janice N. ;

Lewis, Carol ;

Hwu, Wen-Jen ;

Hanna, Ehab ;

Diab, Adi ;

Wong, Michael K. ;

Royal, Richard ;

Gross, Neil ;

Weber, Randal ;

Lai, Stephen Y. ;

Ehlers, Richard ;

Blando, Jorge ;

Milton, Denai R. ;

Woodman, Scott ;

Kageyama, Robin ;

Wells, Daniel K. ;

Hwu, Patrick ;

Patel, Sapna P. ;

Lucci, Anthony ;

Hessel, Amy ;

Lee, Jeffrey E. ;

Gershenwald, Jeffrey ;

Simpson, Lauren ;

Burton, Elizabeth M. ;

Posada, Liberty ;

Haydu, Lauren ;

Wang, Linghua ;

Zhang, Shaojun ;

Lazar, Alexanderj ;

Hudgens, Courtney W. ;

Gopalakrishnan, Vancheswaran ;

Reuben, Alexandre ;

Andrews, Miles C. ;

Spencer, Christine N. ;

Prieto, Victor ;

Sharma, Padmanee ;

Allison, James ;

Tetzlaff, Michael T. ;

Wargo, Jennifer A. .

NATURE MEDICINE, 2018, 24 (11) :1649-+

[2]

[Anonymous], ANN ONCOL S11

[3] Pancreatic stellate cells: a starring role in normal and diseased pancreas [J].

Apte, Minoti V. ;

Pirola, Romano C. ;

Wilson, Jeremy S. .

FRONTIERS IN PHYSIOLOGY, 2012, 3

[4] Identification, culture, and characterization of pancreatic stellate cells in rats and humans [J].

Bachem, MG ;

Schneider, E ;

Gross, H ;

Weidenbach, H ;

Schmid, RM ;

Menke, A ;

Siech, M ;

Beger, H ;

Grünert, A ;

Adler, G .

GASTROENTEROLOGY, 1998, 115 (02) :421-432

[5] Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer [J].

Balachandran, Vinod P. ;

Luksza, Marta ;

Zhao, Julia N. ;

Makarov, Vladimir ;

Moral, John Alec ;

Remark, Romain ;

Herbst, Brian ;

Askan, Gokce ;

Bhanot, Umesh ;

Senbabaoglu, Yasin ;

Wells, Daniel K. ;

Cary, Charles Ian Ormsby ;

Grbovic-Huezo, Olivera ;

Attiyeh, Marc ;

Medina, Benjamin ;

Zhang, Jennifer ;

Loo, Jennifer ;

Saglimbeni, Joseph ;

Abu-Akeel, Mohsen ;

Zappasodi, Roberta ;

Riaz, Nadeem ;

Smoragiewicz, Martin ;

Kelley, Z. Larkin ;

Basturk, Olca ;

Goenen, Mithat ;

Levine, Arnold J. ;

Allen, Peter J. ;

Fearon, Douglas T. ;

Merad, Miriam ;

Gnjatic, Sacha ;

Iacobuzio-Donahue, Christine A. ;

Wolchok, Jedd D. ;

DeMatteo, Ronald P. ;

Chan, Timothy A. ;

Greenbaum, Benjamin D. ;

Merghoub, Taha ;

Leach, Steven D. .

NATURE, 2017, 551 (7681) :512-+

[6] Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer [J].

Bayne, Lauren J. ;

Beatty, Gregory L. ;

Jhala, Nirag ;

Clark, Carolyn E. ;

Rhim, Andrew D. ;

Stanger, Ben Z. ;

Vonderheide, Robert H. .

CANCER CELL, 2012, 21 (06) :822-835

[7] Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6Clow F4/80+ Extratumoral Macrophages [J].

Beatty, Gregory L. ;

Winograd, Rafael ;

Evans, Rebecca A. ;

Long, Kristen B. ;

Luque, Santiago L. ;

Lee, Jae W. ;

Clendenin, Cynthia ;

Gladney, Whitney L. ;

Knoblock, Dawson M. ;

Guirnalda, Patrick D. ;

Vonderheide, Robert H. .

GASTROENTEROLOGY, 2015, 149 (01) :201-210

[8] Helping the CD8+ T-cell response [J].

Bevan, MJ .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (08) :595-602

[9] CD4+ T cell help in cancer immunology and immunotherapy [J].

Borst, Jannie ;

Ahrends, Tomasz ;

Babala, Nikolina ;

Melief, Cornelis J. M. ;

Kastenmueller, Wolfgang .

NATURE REVIEWS IMMUNOLOGY, 2018, 18 (10) :635-647

[10] Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].

Brahmer, Julie R. ;

Tykodi, Scott S. ;

Chow, Laura Q. M. ;

Hwu, Wen-Jen ;

Topalian, Suzanne L. ;

Hwu, Patrick ;

Drake, Charles G. ;

Camacho, Luis H. ;

Kauh, John ;

Odunsi, Kunle ;

Pitot, Henry C. ;

Hamid, Omid ;

Bhatia, Shailender ;

Martins, Renato ;

Eaton, Keith ;

Chen, Shuming ;

Salay, Theresa M. ;

Alaparthy, Suresh ;

Grosso, Joseph F. ;

Korman, Alan J. ;

Parker, Susan M. ;

Agrawal, Shruti ;

Goldberg, Stacie M. ;

Pardoll, Drew M. ;

Gupta, Ashok ;

Wigginton, Jon M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465

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