Culprits of PDAC resistance to gemcitabine and immune checkpoint inhibitor: Tumour microenvironment components

被引：16

作者：

Hsu, Sheng-Kai ^{[1
,2
]}

Jadhao, Mahendra ^{[3
,4
]}

Liao, Wei-Ting ^{[1
]}

Chang, Wen-Tsan ^{[5
,6
,7
]}

Hung, Chun-Tzu ^{[1
]}

Chiu, Chien-Chih ^{[1
,7
,8
,9
,10
]}

机构：

[1] Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan

[2] Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung, Taiwan

[3] Kaohsiung Med Univ, Dept Med & Appl Chem, Kaohsiung, Taiwan

[4] Univ Cincinnati, Dept Canc Biol, Coll Med, Cincinnati, OH USA

[5] Kaohsiung Med Univ Hosp, Dept Surg, Div Gen & Digest Surg, Kaohsiung, Taiwan

[6] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Surg, Kaohsiung, Taiwan

[7] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Ctr Canc Res, Kaohsiung, Taiwan

[8] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung, Taiwan

[9] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan

[10] Natl Lab Anim Ctr, Natl Appl Res Labs, Taipei, Taiwan

来源：

FRONTIERS IN MOLECULAR BIOSCIENCES | 2022年 / 9卷

关键词：

pancreatic ductal adenocarcinoma; tumour microenvironment; desmoplasia; immunomodulation; chemoresistance; ICI resistance; PANCREATIC ADENOCARCINOMA; CELLS; STROMA; IMMUNOTHERAPY; CHEMOTHERAPY; EXOSOMES; PROMOTES; THERAPY;

D O I：

10.3389/fmolb.2022.1020888

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：

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer with a dismal five-year survival rate of 11%. Despite remarkable advancements in cancer therapeutics, PDAC patients rarely benefit from it due to insurmountable treatment resistance. Notably, PDAC is pathologically characterized by an extensive desmoplastic reaction and an extremely immunosuppressive tumour microenvironment (TME). The PDAC TME consists of cell components (e.g., tumour, immune and stromal cells) and noncellular components (e.g., extracellular matrix), exhibiting high complexity and their interplay resulting in resistance to chemotherapeutics and immune checkpoint inhibitors. In our review, we shed light on how crosstalk of complex environmental components modulates PDAC drug resistance, and we summarize related clinical trials. Moreover, we extend our discussion on TME exploration and exosome analysis, providing new insights into clinical applications, including personalized medicine, disease monitoring and drug carriers.

引用

页数：12

共 83 条

[1] Vitamin D Receptor Activation and Photodynamic Priming Enables Durable Low-dose Chemotherapy [J].

Anbil, Sriram ;

Pigula, Michael ;

Huang, Huang-Chiao ;

Mallidi, Srivalleesha ;

Broekgaarden, Mans ;

Baglo, Yan ;

De Silva, Pushpamali ;

Simeone, Diane M. ;

Mino-Kenudson, Mari ;

Maytin, Edward, V ;

Rizvi, Imran ;

Hasan, Tayyaba .

MOLECULAR CANCER THERAPEUTICS, 2020, 19 (06) :1308-1319

[2] 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

[3] Immune checkpoint blockade in hematologic malignancies [J].

Armand, Philippe .

BLOOD, 2015, 125 (22) :3393-3400

[4] Transfer of miRNA in Macrophage-Derived Exosomes Induces Drug Resistance in Pancreatic Adenocarcinoma [J].

Binenbaum, Yoav ;

Fridman, Eran ;

Yaari, Zvi ;

Milman, Neta ;

Schroeder, Avi ;

Ben David, Gil ;

Shlomi, Tomer ;

Gil, Ziv .

CANCER RESEARCH, 2018, 78 (18) :5287-5299

[5] Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer [J].

Blando, Jorge ;

Sharma, Anu ;

Higa, Maria Gisela ;

Zhao, Hao ;

Vence, Luis ;

Yadav, Shalini S. ;

Kim, Jiseong ;

Sepulveda, Alejandro M. ;

Sharp, Michael ;

Maitra, Anirban ;

Wargo, Jennifer ;

Tetzlaff, Michael ;

Broaddus, Russell ;

Katz, Matthew H. G. ;

Varadhachary, Gauri R. ;

Overman, Michael ;

Wang, Huamin ;

Yee, Cassian ;

Bernatchez, Chantale ;

Iacobuzio-Donahue, Christine ;

Basu, Sreyashi ;

Allison, James P. ;

Sharma, Padmanee .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (05) :1692-1697

[6] BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial [J].

Bockorny, Bruno ;

Semenisty, Valerya ;

Macarulla, Teresa ;

Borazanci, Erkut ;

Wolpin, Brian M. ;

Stemmer, Salomon M. ;

Golan, Talia ;

Geva, Ravit ;

Borad, Mitesh J. ;

Pedersen, Katrina S. ;

Park, Joon Oh ;

Ramirez, Robert A. ;

Abad, David G. ;

Feliu, Jaime ;

Munoz, Andres ;

Ponz-Sarvise, Mariano ;

Peled, Amnon ;

Lustig, Tzipora M. ;

Bohana-Kashtan, Osnat ;

Shaw, Stephen M. ;

Sorani, Ella ;

Chaney, Marya ;

Kadosh, Shaul ;

Haras, Abi Vainstein ;

Von Hoff, Daniel D. ;

Hidalgo, Manuel .

NATURE MEDICINE, 2020, 26 (06) :878-+

[7] Perioperative, Spatiotemporally Coordinated Activation of T and NK Cells Prevents Recurrence of Pancreatic Cancer [J].

Brooks, Jennifer ;

Fleischmann-Mundt, Bettina ;

Woller, Norman ;

Niemann, Julia ;

Ribback, Silvia ;

Peters, Kristin ;

Demir, Ihsan Ekin ;

Armbrecht, Nina ;

Ceyhan, Guralp O. ;

Manns, Michael P. ;

Wirth, Thomas C. ;

Kubicka, Stefan ;

Bernhardt, Gunter ;

Smyth, Mark J. ;

Calvisi, Diego F. ;

Guerlevik, Engin ;

Kuehnel, Florian .

CANCER RESEARCH, 2018, 78 (02) :475-488

[8] Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity [J].

Capello, Michela ;

Vykoukal, Jody V. ;

Katayama, Hiroyuki ;

Bantis, Leonidas E. ;

Wang, Hong ;

Kundnani, Deepali L. ;

Aguilar-Bonavides, Clemente ;

Aguilar, Mitzi ;

Tripathi, Satyendra C. ;

Dhillon, Dilsher S. ;

Momin, Amin A. ;

Peters, Haley ;

Katz, Matthew H. ;

Alvarez, Hector ;

Bernard, Vincent ;

Ferri-Borgogno, Sammy ;

Brand, Randall ;

Adler, Douglas G. ;

Firpo, Matthew A. ;

Mulvihill, Sean J. ;

Molldrem, Jeffrey J. ;

Feng, Ziding ;

Taguchi, Ayumu ;

Maitra, Anirban ;

Hanash, Samir M. .

NATURE COMMUNICATIONS, 2019, 10 (1)

[9] Drug resistance in pancreatic cancer: New player caught in act [J].

Capurso, Gabriele ;

Sette, Claudio .

EBIOMEDICINE, 2019, 40 :39-40

[10] Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis [J].

Chin, Venessa T. ;

Vennin, Claire ;

Warren, Sean C. ;

Lucas, Morghan C. ;

Herrmann, David ;

Magenau, Astrid ;

Melenec, Pauline ;

Walters, Stacey N. ;

Monte-Nieto, Gonzalo dl ;

Conway, James R. W. ;

Nobis, Max ;

Allam, Amr H. ;

McCloy, Rachael A. ;

Currey, Nicola ;

Pinese, Mark ;

Boulghourjian, Alice ;

Zaratzian, Anaiis ;

Adam, Arne A. S. ;

Heu, Celine ;

Nagrial, Adnan M. ;

Chou, Angela ;

Steinmann, Angela ;

Drury, Alison ;

Froio, Danielle ;

Giry-Laterriere, Marc ;

Harris, Nathanial L. E. ;

Phan, Tri ;

Jain, Rohit ;

Weninger, Wolfgang ;

McGhee, Ewan J. ;

Whan, Renee ;

Johns, Amber L. ;

Samra, Jaswinder S. ;

Chantrill, Lorraine ;

Gill, Anthony J. ;

Kohonen-Corish, Maija ;

Harvey, Richard P. ;

Biankin, Andrew V. ;

Evans, T. R. Jeffry ;

Anderson, Kurt I. ;

Grey, Shane T. ;

Ormandy, Christopher J. ;

Gallego-Ortega, David ;

Wang, Yingxiao ;

Samuel, Michael S. ;

Sansom, Owen J. ;

Burgess, Andrew ;

Cox, Thomas R. ;

Morton, Jennifer P. ;

Pajic, Marina .

SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (384)

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