Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options

Frontiers in Immunology
Derya KabacaogluHana Algül

Abstract

Pancreatic ductal adenocarcinoma (PDAC), as the most frequent form of pancreatic malignancy, still is associated with a dismal prognosis. Due to its late detection, most patients are ineligible for surgery, and chemotherapeutic options are limited. Tumor heterogeneity and a characteristic structure with crosstalk between the cancer/malignant cells and an abundant tumor microenvironment (TME) make PDAC a very challenging puzzle to solve. Thus far, targeted therapies have failed to substantially improve the overall survival of PDAC patients. Immune checkpoint inhibition, as an emerging therapeutic option in cancer treatment, shows promising results in different solid tumor types and hematological malignancies. However, PDAC does not respond well to immune checkpoint inhibitors anti-programmed cell death protein 1 (PD-1) or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) alone or in combination. PDAC with its immune-privileged nature, starting from the early pre-neoplastic state, appears to escape from the antitumor immune response unlike other neoplastic entities. Different mechanisms how cancer cells achieve immune-privileged status have been hypothesized. Among them are decreased antigenicity and impaired immunogenici...Continue Reading

References

Jan 1, 1971·Transplantation Reviews·F M Burnet
May 1, 1996·Scandinavian Journal of Immunology·S LohmannB Seliger
Jun 1, 1996·The Journal of Experimental Medicine·M F Krummel, J P Allison
Jul 7, 1998·The Journal of Experimental Medicine·F FallarinoT F Gajewski
Nov 10, 1998·European Journal of Immunology·C A ChambersJ P Allison
May 4, 1999·The Journal of Experimental Medicine·D H MunnA L Mellor
Feb 27, 2001·Nature Immunology·Y LatchmanG J Freeman
Mar 21, 2001·The Journal of Experimental Medicine·E Y LinJ W Pollard
Apr 3, 2001·The Journal of Experimental Medicine·S Y TsengH Tsuchiya
Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Aug 2, 2002·Cancer Cell·Elizabeth M JaffeeScott E Kern
Sep 17, 2002·Cell Death and Differentiation·F FallarinoP Puccetti
Oct 31, 2002·Nature Immunology·Gavin P DunnRobert D Schreiber
Jan 11, 2003·Science·Shohei HoriShimon Sakaguchi
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Jul 9, 2003·The Journal of Experimental Medicine·Yoshiko IwaiTasuku Honjo
Jan 7, 2004·Cancer Cell·Sunil R HingoraniDavid A Tuveson
Jan 20, 2004·Cancer Research·Felix HerrmannBarbara Seliger
Mar 23, 2004·Annual Review of Immunology·Sergio A QuezadaRandolph J Noelle
Mar 23, 2004·Annual Review of Immunology·Gavin P DunnRobert D Schreiber
May 10, 2005·Nature Medicine·Nicole C KaneiderAthan Kuliopulos
Jun 14, 2005·Nature Immunology·Gavin P DunnRobert D Schreiber
Sep 28, 2005·The Journal of Experimental Medicine·Paulo C RodriguezAugusto C Ochoa
Sep 27, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nobuyoshi HiraokaSetsuo Hirohashi

❮ Previous
Next ❯

Citations

Oct 16, 2019·The Journal of Clinical Investigation·Nikita S SharmaSulagna Banerjee
Mar 5, 2020·International Journal of Cancer. Journal International Du Cancer·Sebastian LundgrenArtur Mezheyeuski
Jul 15, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·P L SmithA G Dalgleish
Mar 7, 2020·Digestive Diseases and Sciences·Jia Wu, Jianting Cai
May 13, 2020·Nature Reviews. Gastroenterology & Hepatology·Abdel N HoseinAnirban Maitra
Aug 23, 2020·Cancers·Didem SakaHande Asimgil
Apr 30, 2020·Cells·Kıvanç GörgülüHana Algül
Sep 16, 2020·British Journal of Cancer·Max PiffouxPhilippe A Cassier
Oct 17, 2020·Journal of Thrombosis and Haemostasis : JTH·Patrick G SchweickertStephen F Konieczny
Oct 23, 2020·Physics in Medicine and Biology·Damijan Valentinuzzi, Robert Jeraj
Jul 22, 2019·Cancer Treatment Reviews·Andreas HenriksenDorte Nielsen
Nov 25, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Olamide T OlaobaKehinde S Ayinde
Jan 26, 2021·Cellular Oncology (Dordrecht)·Axel BengtssonDaniel Ansari
Jan 19, 2020·Seminars in Immunology·Shailendra K GautamSurinder K Batra
Nov 15, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·M E LorkowskiE Karathanasis
Mar 7, 2021·International Journal of Molecular Sciences·Yolanda Rodríguez GilVíctor Javier Sánchez-Arévalo Lobo
Mar 19, 2021·Expert Opinion on Emerging Drugs·Jasmeet KaurVaibhav Sahai
Mar 21, 2021·Communications Biology·Amanda Rosewell ShawMasataka Suzuki
Apr 30, 2021·Immunotherapy·Jasmeet KaurRafiullah Khan
Jun 3, 2021·Immunological Reviews·Mélanie Desbois, Yulei Wang
Jun 3, 2021·International Journal of Molecular Sciences·Aditi Kothari, Matthew J Flick
Jul 8, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Miar ElaskandranyAnjana Saxena
Sep 17, 2021·Current Cancer Drug Targets·Anna KasperskaŁukasz Szylber

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Methods Mentioned

BETA
transgenic
surgical resection

Clinical Trials Mentioned

NCT02758587
NCT03193190
NCT02472977
NCT02826486
NCT02907099
NCT03168139
NCT03481920
NCT03331562
NCT02304393
NCT02526017

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