Cold Tumors: A Therapeutic Challenge for Immunotherapy

Frontiers in Immunology
Paola BonaventuraStéphane Depil

Abstract

Therapeutic monoclonal antibodies targeting immune checkpoints (ICPs) have changed the treatment landscape of many tumors. However, response rate remains relatively low in most cases. A major factor involved in initial resistance to ICP inhibitors is the lack or paucity of tumor T cell infiltration, characterizing the so-called "cold tumors." In this review, we describe the main mechanisms involved in the absence of T cell infiltration, including lack of tumor antigens, defect in antigen presentation, absence of T cell activation and deficit of homing into the tumor bed. We discuss then the different therapeutic approaches that could turn cold into hot tumors. In this way, specific therapies are proposed according to their mechanism of action. In addition, ''supra-physiological'' therapies, such as T cell recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, may be active regardless of the mechanism involved, especially in MHC class I negative tumors. The determination of the main factors implicated in the lack of preexisting tumor T cell infiltration is crucial for the development of adapted algorithms of treatments for cold tumors.

References

Mar 29, 2001·Nature Immunology·S A Luther, J G Cyster
Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Jul 22, 2004·British Journal of Cancer·R F M BeversD H J Schamhart
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Steven A RosenbergSeth M Steinberg
Feb 14, 2006·Cell Research·Rashu B SethZhijian J Chen
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
May 13, 2006·Nature Reviews. Immunology·Caetano Reis e Sousa
Nov 30, 2007·Annual Review of Immunology·Gwendalyn J RandolphSantiago Partida-Sánchez
Sep 20, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Marie-Caroline Dieu-NosjeanJacques Cadranel
Feb 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Carmine CarpenitoCarl H June
Mar 19, 2009·Cancer Research·Helena HarlinThomas F Gajewski
Apr 15, 2009·Nature Reviews. Immunology·Douglas R GreenGuido Kroemer
May 19, 2009·Cancer Immunology, Immunotherapy : CII·Evelien L J M SmitsViggo F I Van Tendeloo
May 19, 2010·The Journal of Experimental Medicine·Sarah L JongbloedKristen J Radford
Aug 4, 2010·Current Topics in Microbiology and Immunology·Lana E KandalaftGeorge Coukos
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joshua D BrodyRonald Levy
Jun 24, 2011·Cancer Research·Sana Intidhar Labidi-GalyNathalie Bendriss-Vermare
Sep 21, 2011·The Journal of Experimental Medicine·Mercedes B FuertesThomas F Gajewski
Sep 21, 2011·The Journal of Experimental Medicine·Barbara MolonAntonella Viola
Jul 12, 2012·Nature Biotechnology·Stephen J RussellJohn C Bell
Jul 19, 2012·International Reviews of Immunology·Andrea KhongBruce W S Robinson
Nov 20, 2012·Annual Review of Immunology·Guido KroemerLaurence Zitvogel
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Aug 13, 2013·Oncogene·J-P PradereR F Schwabe
Sep 21, 2013·Nature Immunology·Thomas F GajewskiYang-Xin Fu
Jan 25, 2014·Nature Reviews. Cancer·Pierre G CoulieThierry Boon
Feb 12, 2014·Cancer Immunology, Immunotherapy : CII·Witold LasekMarek Jakobisiak
Apr 5, 2014·Oncoimmunology·Fernando ArandaLorenzo Galluzzi
Jul 19, 2014·Nature Reviews. Immunology·Martin GuilliamsSimon Yona
Dec 8, 2014·Seminars in Radiation Oncology·Encouse B Golden, Lionel Apetoh
Mar 3, 2015·Drug Discovery Today·Roland E Kontermann, Ulrich Brinkmann

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Citations

Jul 20, 2019·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Zhengxian HuangCheng Wang
Jan 19, 2020·Cancer Immunology, Immunotherapy : CII·Michael HaderUdo S Gaipl
Jan 16, 2020·Journal of Clinical Medicine·Masmudur M Rahman, Grant McFadden
Oct 18, 2019·Journal for Immunotherapy of Cancer·Tae Heung KangChien-Fu Hung
Feb 6, 2020·Scandinavian Journal of Immunology·Liam Pock HoKheng Wei Yeoh
Mar 25, 2020·American Society of Clinical Oncology Educational Book·Evan T HallShailender Bhatia
Aug 20, 2019·Photochemistry and Photobiology·Eric M KercherBryan Q Spring
Apr 2, 2020·Expert Opinion on Therapeutic Targets·Christopher LarsonTony R Reid
Jul 2, 2019·Oncotarget·Stéphane DepilVincent Alcazer
May 16, 2020·Nature Biomedical Engineering·Jürgen Scheller, Philipp A Lang
Jun 1, 2020·Journal for Immunotherapy of Cancer·Laura-Sophie LandwehrSilviu Sbiera
Jul 22, 2020·Journal for Immunotherapy of Cancer·María Alejandra GleisnerFlavio Salazar-Onfray
Jul 6, 2020·International Immunology·Alok Kumar, Kenji Chamoto
Oct 17, 2019·Cold Spring Harbor Perspectives in Medicine·Jong-Ho ChaMien-Chie Hung
Sep 24, 2020·Immunological Reviews·Chirine RafiaEmmanuel Scotet
Oct 1, 2020·Clinical & Translational Immunology·Synat KeamAlistair M Cook
Jun 9, 2020·Frontiers in Immunology·Jörg WischhusenWolf Herman Fridman
May 22, 2020·Cancer Metastasis Reviews·Pablo Lopez-Bergami, Gastón Barbero
Jul 17, 2020·Frontiers in Immunology·Philippe RochigneuxEdward B Garon
Jun 20, 2020·Journal of Leukocyte Biology·Sohini RoyDouglas B Johnson
Aug 28, 2020·Signal Transduction and Targeted Therapy·Ming-Zhu Jin, Wei-Lin Jin
Jul 24, 2020·Cellular & Molecular Immunology·Xingyi Pan, Lei Zheng
Jul 24, 2020·Cellular & Molecular Immunology·Dieter KabelitzShirin Kalyan
Sep 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Soehartati A GondhowiardjoAngela Giselvania
Mar 3, 2020·Frontiers in Immunology·Sara SaabHumam Kadara
Apr 10, 2020·JCI Insight·Nirmish SinglaJames Brugarolas
Mar 3, 2020·Frontiers in Immunology·Eric D RouthLance D Miller
Sep 27, 2019·The FEBS Journal·Andrés Lanzós, Kerryn Elliott
Feb 28, 2020·Cancers·Celina L SzantoStefan Nierkens
Sep 26, 2020·Cancer Cell International·Seyed Mohammad MiriAmir Ghaemi
Sep 4, 2020·PLoS Pathogens·Dohun PyeonJoseph A Westrich
May 7, 2020·BMC Immunology·Milene PetersonStephen Albert Johnston
Sep 18, 2020·Cells·Lena GaissmaierPetros Christopoulos
Feb 1, 2020·Current Pharmaceutical Design·Khanh B TranPeter R Shepherd
Apr 1, 2020·Frontiers in Oncology·Valentina BrunoEnrico Vizza

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