. 2019 Oct;574(7776).
doi: 10.1038/s41586-019-1593-5.

Harnessing innate immunity in cancer therapy

Olivier Demaria 1 Stéphanie Cornen 1 Marc Daëron 2 Yannis Morel 1 Ruslan Medzhitov 3 Eric Vivier 4 
  • PMID: 31578484
  •     201 References
  •     76 citations


New therapies that promote antitumour immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy. Given the crucial role of innate immune responses in immunity, harnessing these responses opens up new possibilities for long-lasting, multilayered tumour control.

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Lawrence P Andrews, Ariel E Marciscano, Charles G Drake, Dario A A Vignali.
Immunol Rev, 2017 Mar 05; 276(1). PMID: 28258692    Free PMC article.
Highly Cited. Review.
Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells.
Theodore Kouo, Lanqing Huang, +4 authors, Elizabeth Jaffee.
Cancer Immunol Res, 2015 Feb 19; 3(4). PMID: 25691328    Free PMC article.
Highly Cited.
Desorption chemical ionization mass spectrometry of anthracyclines and of trisaccharides related to aclacinomycin A and marcellomycin.
C Monneret, N Sellier.
Biomed Environ Mass Spectrom, 1986 Jul 01; 13(7). PMID: 2943345
Myeloid-derived suppressor cells as regulators of the immune system.
Dmitry I Gabrilovich, Srinivas Nagaraj.
Nat Rev Immunol, 2009 Feb 07; 9(3). PMID: 19197294    Free PMC article.
Highly Cited. Review.
Macrophages and therapeutic resistance in cancer.
Brian Ruffell, Lisa M Coussens.
Cancer Cell, 2015 Apr 11; 27(4). PMID: 25858805    Free PMC article.
Highly Cited. Review.
Myeloid-Derived Suppressor Cells.
Dmitry I Gabrilovich.
Cancer Immunol Res, 2017 Jan 06; 5(1). PMID: 28052991    Free PMC article.
Highly Cited. Review.
Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment.
Caglar Cekic, Yuan-Ji Day, Duygu Sag, Joel Linden.
Cancer Res, 2014 Nov 08; 74(24). PMID: 25377469    Free PMC article.
Highly Cited.
High hopes and high honours for cancer immunotherapy.
Sophia Julia Häfner.
Biomed J, 2019 Dec 01; 42(5). PMID: 31783989    Free PMC article.
Spatio-temporal aspects of the interplay of cancer and the immune system.
Vladimir P Zhdanov.
J Biol Phys, 2019 Nov 28; 45(4). PMID: 31773382    Free PMC article.
Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer.
Jie Wang, Xiaobo Bo, +13 authors, Houbao Liu.
Cancer Sci, 2019 Nov 16; 111(1). PMID: 31729088    Free PMC article.
Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword.
Qiutong Huang, Wang Cao, +3 authors, Nicolas Jacquelot.
Front Immunol, 2020 Feb 06; 10. PMID: 32010138    Free PMC article.
RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer.
Maria Gabriela-Freitas, Joana Pinheiro, +2 authors, Olga Martinho.
Biomolecules, 2019 Nov 27; 9(12). PMID: 31766768    Free PMC article.
Helper Innate Lymphoid Cells in Human Tumors: A Double-Edged Sword?
Nicola Tumino, Paola Vacca, +5 authors, Lorenzo Moretta.
Front Immunol, 2020 Feb 18; 10. PMID: 32063901    Free PMC article.
TYK2 in Tumor Immunosurveillance.
Anzhelika Karjalainen, Stephen Shoebridge, +5 authors, Mathias Müller.
Cancers (Basel), 2020 Jan 16; 12(1). PMID: 31936322    Free PMC article.
The Crosstalk Between Hippo-YAP Pathway and Innate Immunity.
Shuai Wang, Lili Zhou, +4 authors, Fangfang Zhou.
Front Immunol, 2020 Mar 17; 11. PMID: 32174922    Free PMC article.
Tumour travel tours - Why circulating cancer cells value company.
Sophia Julia Häfner.
Biomed J, 2020 Mar 24; 43(1). PMID: 32200951    Free PMC article.
Prostaglandin E Receptor 4 Antagonist in Cancer Immunotherapy: Mechanisms of Action.
Yukinori Take, Shinichi Koizumi, Atsushi Nagahisa.
Front Immunol, 2020 Mar 27; 11. PMID: 32210957    Free PMC article.
BRD4 inhibition exerts anti-viral activity through DNA damage-dependent innate immune responses.
Jiang Wang, Guo-Li Li, +13 authors, Bei-Bei Chu.
PLoS Pathog, 2020 Mar 26; 16(3). PMID: 32208449    Free PMC article.
The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities.
Melissa Alame, Emmanuel Cornillot, +11 authors, Jacques Colinge.
Theranostics, 2020 Apr 16; 10(10). PMID: 32292502    Free PMC article.
Understanding innate immune response in glioblastoma in search of a way forward.
Ayush Pant, Michael Lim.
Neuro Oncol, 2020 Feb 25; 22(4). PMID: 32090256    Free PMC article.
Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers.
M Segovia, S Russo, +2 authors, M Hill.
Clin Exp Immunol, 2020 Apr 17; 200(2). PMID: 32297328    Free PMC article.
Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli-an Industry Perspective.
Jun Xu, Robert Saklatvala, +2 authors, Adam Procopio.
Adv Sci (Weinh), 2020 Apr 25; 7(8). PMID: 32328428    Free PMC article.
Immune Suppression in Pregnancy and Cancer: Parallels and Insights.
Irina Kareva.
Transl Oncol, 2020 May 01; 13(7). PMID: 32353791    Free PMC article.
MR1-Restricted T Cells Are Unprecedented Cancer Fighters.
Alessandro Vacchini, Andrew Chancellor, +2 authors, Gennaro De Libero.
Front Immunol, 2020 May 16; 11. PMID: 32411144    Free PMC article.
Directed Differentiation of Mobilized Hematopoietic Stem and Progenitor Cells into Functional NK cells with Enhanced Antitumor Activity.
Pranav Oberoi, Kathrina Kamenjarin, +3 authors, Winfried S Wels.
Cells, 2020 Apr 02; 9(4). PMID: 32230942    Free PMC article.
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies.
Florent Petitprez, Maxime Meylan, +2 authors, Wolf H Fridman.
Front Immunol, 2020 May 28; 11. PMID: 32457745    Free PMC article.
Bispecific antibodies in cancer immunotherapy.
Christoph Rader.
Curr Opin Biotechnol, 2019 Dec 17; 65. PMID: 31841859    Free PMC article.
Selective reactivation of STING signaling to target Merkel cell carcinoma.
Wei Liu, Gloria B Kim, +3 authors, Jianxin You.
Proc Natl Acad Sci U S A, 2020 Jun 03; 117(24). PMID: 32482869    Free PMC article.
Generation of Myeloid Cells in Cancer: The Spleen Matters.
Chong Wu, Qiaomin Hua, Limin Zheng.
Front Immunol, 2020 Jun 26; 11. PMID: 32582203    Free PMC article.
Extracellular Vesicles Mediate B Cell Immune Response and Are a Potential Target for Cancer Therapy.
Taketo Kato, Johannes F Fahrmann, Samir M Hanash, Jody Vykoukal.
Cells, 2020 Jun 26; 9(6). PMID: 32580358    Free PMC article.
Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors.
Jesper Geert Pedersen, Anne Tranberg Madsen, +4 authors, Martin Roelsgaard Jakobsen.
Cancers (Basel), 2020 Jun 04; 12(6). PMID: 32486146    Free PMC article.
Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy.
Pierpaolo Ginefra, Girieca Lorusso, Nicola Vannini.
Int J Mol Sci, 2020 Jun 26; 21(12). PMID: 32580431    Free PMC article.
Organoid Models of Tumor Immunology.
Kanako Yuki, Ning Cheng, Michitaka Nakano, Calvin J Kuo.
Trends Immunol, 2020 Jul 14; 41(8). PMID: 32654925    Free PMC article.
Combinatorial Immunotherapies for Metastatic Colorectal Cancer.
Eline Janssen, Beatriz Subtil, +2 authors, Daniele V F Tauriello.
Cancers (Basel), 2020 Jul 16; 12(7). PMID: 32664619    Free PMC article.
The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications.
Yuanyuan Zhang, Zemin Zhang.
Cell Mol Immunol, 2020 Jul 03; 17(8). PMID: 32612154    Free PMC article.
RNA Recognition and Immunity-Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms.
Takuya Uehata, Osamu Takeuchi.
Cells, 2020 Jul 28; 9(7). PMID: 32708595    Free PMC article.
Uncovering the Exosomes Diversity: A Window of Opportunity for Tumor Progression Monitoring.
Domenico Maisano, Selena Mimmi, +6 authors, Enrico Iaccino.
Pharmaceuticals (Basel), 2020 Aug 08; 13(8). PMID: 32759810    Free PMC article.
Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis.
Baihui Li, Bailu Zhang, +6 authors, Lili Yang.
Oncoimmunology, 2020 Sep 18; 9(1). PMID: 32939323    Free PMC article.
Innate immune checkpoints for cancer immunotherapy: expanding the scope of non T cell targets.
Luis F Campesato, Chien-Huan Weng, Taha Merghoub.
Ann Transl Med, 2020 Sep 22; 8(16). PMID: 32953831    Free PMC article.
Nanoparticles Presenting Potent TLR7/8 Agonists Enhance Anti-PD-L1 Immunotherapy in Cancer Treatment.
Anton A A Smith, Emily C Gale, +4 authors, Eric A Appel.
Biomacromolecules, 2020 Aug 21; 21(9). PMID: 32816460    Free PMC article.
Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death.
Wei Yang, Zenghe Xiu, +3 authors, Ting Sun.
Cell Death Dis, 2020 Sep 24; 11(9). PMID: 32963254    Free PMC article.
A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality.
Rima Hajjo, Alexander Tropsha.
Pharm Res, 2020 Oct 08; 37(11). PMID: 33025261    Free PMC article.
Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis.
Lang Rao, Lei Wu, +15 authors, Xiaoyuan Chen.
Nat Commun, 2020 Oct 02; 11(1). PMID: 32999291    Free PMC article.
Unique immunological profile in patients with COVID-19.
Stefania Varchetta, Dalila Mele, +11 authors, Mario U Mondelli.
Cell Mol Immunol, 2020 Oct 17; 18(3). PMID: 33060840    Free PMC article.
Nano-Enhanced Cancer Immunotherapy: Immunology Encounters Nanotechnology.
Ernesto Bockamp, Sebastian Rosigkeit, Dominik Siegl, Detlef Schuppan.
Cells, 2020 Sep 19; 9(9). PMID: 32942725    Free PMC article.
Airway Natural Killer Cells and Bacteria in Health and Disease.
Maud Theresine, Neha D Patil, Jacques Zimmer.
Front Immunol, 2020 Oct 27; 11. PMID: 33101315    Free PMC article.
Female Malignancies and Immunotherapy: What's New?
Silvia Pesce, Valerio Gaetano Vellone, Emanuela Marcenaro.
Cancers (Basel), 2020 Oct 15; 12(10). PMID: 33050485    Free PMC article.
Cancer immunotherapy with γδ T cells: many paths ahead of us.
Dieter Kabelitz, Ruben Serrano, +2 authors, Shirin Kalyan.
Cell Mol Immunol, 2020 Jul 24; 17(9). PMID: 32699351    Free PMC article.
Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses.
Katherine J Brempelis, Courtney M Cowan, +21 authors, Courtney A Crane.
J Immunother Cancer, 2020 Oct 30; 8(2). PMID: 33115946    Free PMC article.
Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies.
Sergi Benavente, Almudena Sánchez-García, +2 authors, Juan Lorente.
Front Oncol, 2020 Nov 17; 10. PMID: 33194719    Free PMC article.
New insights into the interaction of the immune system with non-small cell lung carcinomas.
Paul Hofman.
Transl Lung Cancer Res, 2020 Nov 20; 9(5). PMID: 33209644    Free PMC article.
Pairwise Stimulations of Pathogen-Sensing Pathways Predict Immune Responses to Multi-adjuvant Combinations.
Surya Pandey, Adam Gruenbaum, +3 authors, Nicolas Chevrier.
Cell Syst, 2020 Oct 29; 11(5). PMID: 33113356    Free PMC article.
Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies.
Miaoqin Chen, Shiman Hu, +3 authors, Lifeng Feng.
Signal Transduct Target Ther, 2020 Nov 21; 5(1). PMID: 33214545    Free PMC article.
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?
Mustafa Khasraw, David A Reardon, Michael Weller, John H Sampson.
Clin Cancer Res, 2020 Jun 13; 26(20). PMID: 32527943    Free PMC article.
Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles.
Lang Rao, Shu-Kun Zhao, +12 authors, Xiaoyuan Chen.
Adv Mater, 2020 Oct 23; 32(47). PMID: 33089578    Free PMC article.
Regulation of cGAS- and RLR-mediated immunity to nucleic acids.
Andrea Ablasser, Sun Hur.
Nat Immunol, 2019 Dec 11; 21(1). PMID: 31819255
Targeting immunogenic cell death in cancer.
Asma Ahmed, Stephen W G Tait.
Mol Oncol, 2020 Nov 13; 14(12). PMID: 33179413    Free PMC article.
PBRM1 and the glycosylphosphatidylinositol biosynthetic pathway promote tumor killing mediated by MHC-unrestricted cytotoxic lymphocytes.
Bridget L Menasche, Eric M Davis, +4 authors, Jingshi Shen.
Sci Adv, 2020 Nov 29; 6(48). PMID: 33246952    Free PMC article.
Pathogen-like Nanoassemblies of Covalently Linked TLR Agonists Enhance CD8 and NK Cell-Mediated Antitumor Immunity.
Saikat Manna, Sampa Maiti, +2 authors, Aaron P Esser-Kahn.
ACS Cent Sci, 2020 Dec 05; 6(11). PMID: 33274283    Free PMC article.
Targeting NK Cell Inhibitory Receptors for Precision Multiple Myeloma Immunotherapy.
Helmi Alfarra, Jackson Weir, Stacy Grieve, Tony Reiman.
Front Immunol, 2020 Dec 12; 11. PMID: 33304346    Free PMC article.
TGFβ-Directed Therapeutics: 2020.
Beverly A Teicher.
Pharmacol Ther, 2020 Aug 25; 217. PMID: 32835827    Free PMC article.
CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration.
Mingsu Shi, Yun Gu, +14 authors, Weijuan Zhang.
Cancer Immunol Immunother, 2021 Jan 04;. PMID: 33389016
Highlighting the Potential for Chronic Stress to Minimize Therapeutic Responses to Radiotherapy through Increased Immunosuppression and Radiation Resistance.
Minhui Chen, Anurag K Singh, Elizabeth A Repasky.
Cancers (Basel), 2021 Jan 10; 12(12). PMID: 33419318    Free PMC article.
The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway.
Rilin Deng, Chaohui Zuo, +24 authors, Haizhen Zhu.
Cell Mol Immunol, 2020 Sep 24; 17(11). PMID: 32963356    Free PMC article.
Molecular Imaging of Immunity and Inflammation and Its Impact on Precision Medicine.
Moritz Wildgruber, Michel Eisenblätter.
Biomedicines, 2021 Jan 15; 9(1). PMID: 33440667    Free PMC article.
In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis.
Seohyun Kim, Seong A Kim, +9 authors, In-San Kim.
J Immunother Cancer, 2021 Jan 23; 9(1). PMID: 33479026    Free PMC article.
SARS-CoV-2 infection: The role of PD-1/PD-L1 and CTLA-4 axis.
Parisa Shiri Aghbash, Narges Eslami, +2 authors, Hossein Bannazadeh Baghi.
Life Sci, 2021 Jan 29; 270. PMID: 33508291    Free PMC article.
Serum cytokine profiles in healthy nonhuman primates are blunted by sedation and demonstrate sexual dimorphism as detected by a validated multiplex immunoassay.
Laura Hocum Stone, Scott Hunter Oppler, +6 authors, Melanie L Graham.
Sci Rep, 2021 Jan 29; 11(1). PMID: 33504894    Free PMC article.
Driving Immune Responses in the Ovarian Tumor Microenvironment.
Franklin Ning, Christopher B Cole, Christina M Annunziata.
Front Oncol, 2021 Feb 02; 10. PMID: 33520713    Free PMC article.
Role of Methylation in Pro- and Anti-Cancer Immunity.
Ali Mehdi, Shafaat A Rabbani.
Cancers (Basel), 2021 Feb 05; 13(3). PMID: 33535484    Free PMC article.
Comprehensive Characterization of Immunological Profiles and Clinical Significance in Hepatocellular Carcinoma.
Ping Tao, Liang Hong, +5 authors, Ruyi Xue.
Front Oncol, 2021 Feb 09; 10. PMID: 33552954    Free PMC article.
A STING-related prognostic score predicts high-risk patients of colorectal cancer and provides insights into immunotherapy.
Si-Yuan Chen, Siyu Chen, +3 authors, Xiaodong Zhu.
Ann Transl Med, 2021 Feb 09; 9(1). PMID: 33553307    Free PMC article.
HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression.
Xiaolei Li, Xiao Su, +8 authors, Yufang Shi.
Oncogene, 2021 Feb 11; 40(10). PMID: 33564072    Free PMC article.
Tailoring precision immunotherapy: coming to a clinic soon?
Shuting Han, Wai Ho Shuen, +2 authors, Han Chong Toh.
ESMO Open, 2021 Feb 10; 5 Suppl 1. PMID: 33558033    Free PMC article.
Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy.
Cheng-Tao Jiang, Kai-Ge Chen, +11 authors, Jun Wang.
Nat Commun, 2021 Mar 03; 12(1). PMID: 33649336    Free PMC article.
Pharmacological Activation of p53 during Human Monocyte to Macrophage Differentiation Attenuates Their Pro-Inflammatory Activation by TLR4, TLR7 and TLR8 Agonists.
Dmitry Namgaladze, Bernhard Brüne.
Cancers (Basel), 2021 Mar 07; 13(5). PMID: 33668835    Free PMC article.
Insights Into the Involvement of Circular RNAs in Autoimmune Diseases.
Xingyu Zhai, Yunfei Zhang, +2 authors, Jianhong Lu.
Front Immunol, 2021 Mar 16; 12. PMID: 33717126    Free PMC article.
The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms.
Yoo Jane Han, Jing Zhang, +10 authors, Olufunmilayo I Olopade.
Cancer Res, 2021 Jan 22; 81(6). PMID: 33472891    Free PMC article.
Activated B lymphocytes and tumor cell lysate as an effective cellular cancer vaccine.
Kyp L Oxley, Brett M Hanson, Ashley N Zani, Gail A Bishop.
Cancer Immunol Immunother, 2021 Mar 26;. PMID: 33765210
Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses.
Jesper van Eck van der Sluijs, Diede van Ens, +13 authors, Willemijn Hobo.
Cancer Immunol Immunother, 2021 Apr 03;. PMID: 33796917
Blood CD3-(CD56 or 16)+ natural killer cell distributions are heterogeneous in healthy adults and suppressed by azathioprine in patients with ANCA-associated vasculitides.
Wolfgang Merkt, Ulrich Salzer, +4 authors, Nils Venhoff.
BMC Immunol, 2021 Apr 13; 22(1). PMID: 33840389    Free PMC article.
Role of kynurenine in promoting the generation of exhausted CD8+ T cells in colorectal cancer.
Dandan Wu, Yufeng Zhu.
Am J Transl Res, 2021 Apr 13; 13(3). PMID: 33841677    Free PMC article.
Turning cold tumors into hot tumors by improving T-cell infiltration.
Yuan-Tong Liu, Zhi-Jun Sun.
Theranostics, 2021 Apr 17; 11(11). PMID: 33859752    Free PMC article.