Review
. 2020 Aug; 11:1633.
doi: 10.3389/fimmu.2020.01633.

Re-education of the Tumor Microenvironment With Targeted Therapies and Immunotherapies

Shin Foong Ngiow 1 Arabella Young 2 
Affiliations
  • PMID: 32849557
  •     181 References
  •     11 citations

Abstract

The clinical success of cancer immunotherapies targeting PD-1 and CTLA-4 has ignited a substantial research effort to improve our understanding of tumor immunity. Recent studies have revealed that the immune contexture of a tumor influences therapeutic response and survival benefit for cancer patients. Identifying treatment modalities that limit immunosuppression, relieve T cell exhaustion, and potentiate effector functions in the tumor microenvironment (TME) is of much interest. In particular, combinatorial therapeutic approaches that re-educate the TME by limiting the accumulation of immunosuppressive immune cells, such as Foxp3 regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), while promoting CD8+ and CD4+ effector T cell activity is critical. Here, we review key approaches to target these immunosuppressive immune cell subsets and signaling molecules and define the impact of these changes to the tumor milieu. We will highlight the preclinical and clinical evidence for their ability to improve anti-tumor immune responses as well as strategies and challenges for their implementation. Together, this review will provide understanding of therapeutic approaches to efficiently shape the TME and reinvigorate the immune response against cancer.

Keywords: adenosine; immune toxicity; mucosal-associated invariant T (MAIT) cells; natural killer T (NKT) cells; prostaglandin; regulatory T cells (Tregs); transforming growth factor (TGF)β; tumor-associated myeloid cells.

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Cancer Immunol Immunother, 2010 May 19; 59(9). PMID: 20480365
MR1 presents microbial vitamin B metabolites to MAIT cells.
Lars Kjer-Nielsen, Onisha Patel, +17 authors, James McCluskey.
Nature, 2012 Oct 12; 491(7426). PMID: 23051753
Highly Cited.
Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis.
Rajeev K Shrimali, Shamim Ahmad, +12 authors, Samir N Khleif.
Cancer Immunol Res, 2017 Aug 30; 5(9). PMID: 28848055
Highly Cited.
Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy.
Rajani Ravi, Kimberly A Noonan, +13 authors, Atul Bedi.
Nat Commun, 2018 Feb 23; 9(1). PMID: 29467463    Free PMC article.
Highly Cited.
MAIT cells are activated during human viral infections.
Bonnie van Wilgenburg, Iris Scherwitzl, +24 authors, Paul Klenerman.
Nat Commun, 2016 Jun 24; 7. PMID: 27337592    Free PMC article.
Highly Cited.
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
V Gopalakrishnan, C N Spencer, +67 authors, J A Wargo.
Science, 2017 Nov 04; 359(6371). PMID: 29097493    Free PMC article.
Highly Cited.
TIGIT predominantly regulates the immune response via regulatory T cells.
Sema Kurtulus, Kaori Sakuishi, +6 authors, Ana C Anderson.
J Clin Invest, 2015 Sep 29; 125(11). PMID: 26413872    Free PMC article.
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IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39.
Ivan D Mascanfroni, Ada Yeste, +10 authors, Francisco J Quintana.
Nat Immunol, 2013 Sep 03; 14(10). PMID: 23995234    Free PMC article.
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George C Prendergast, Courtney Smith, +4 authors, Alexander J Muller.
Cancer Immunol Immunother, 2014 Apr 09; 63(7). PMID: 24711084    Free PMC article.
Highly Cited. Review.
Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors.
Vinit Kumar, Laxminarasimha Donthireddy, +27 authors, Dmitry I Gabrilovich.
Cancer Cell, 2017 Nov 15; 32(5). PMID: 29136508    Free PMC article.
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Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy.
Mehmet Asim Bilen, Julie M Shabto, +17 authors, R Donald Harvey.
BMC Cancer, 2019 Aug 30; 19(1). PMID: 31464611    Free PMC article.
Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
Ayelet Sivan, Leticia Corrales, +9 authors, Thomas F Gajewski.
Science, 2015 Nov 07; 350(6264). PMID: 26541606    Free PMC article.
Highly Cited.
Blocking the CCL2-CCR2 Axis Using CCL2-Neutralizing Antibody Is an Effective Therapy for Hepatocellular Cancer in a Mouse Model.
Kun-Yu Teng, Jianfeng Han, +10 authors, Kalpana Ghoshal.
Mol Cancer Ther, 2016 Dec 17; 16(2). PMID: 27980102    Free PMC article.
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Stephen M Hatfield, Jorgen Kjaergaard, +15 authors, Michail Sitkovsky.
J Mol Med (Berl), 2014 Aug 15; 92(12). PMID: 25120128    Free PMC article.
Tumor Mutational Burden and Response Rate to PD-1 Inhibition.
Mark Yarchoan, Alexander Hopkins, Elizabeth M Jaffee.
N Engl J Med, 2017 Dec 21; 377(25). PMID: 29262275    Free PMC article.
Highly Cited.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
Jedd D Wolchok, Vanna Chiarion-Sileni, +30 authors, James Larkin.
N Engl J Med, 2017 Sep 12; 377(14). PMID: 28889792    Free PMC article.
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Emmanuel Treiner, Livine Duban, +6 authors, Olivier Lantz.
Nature, 2003 Mar 14; 422(6928). PMID: 12634786
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The immune contexture in human tumours: impact on clinical outcome.
Wolf Herman Fridman, Franck Pagès, Catherine Sautès-Fridman, Jérôme Galon.
Nat Rev Cancer, 2012 Mar 16; 12(4). PMID: 22419253
Highly Cited. Review.
The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine.
J Blay, T D White, D W Hoskin.
Cancer Res, 1997 Jul 01; 57(13). PMID: 9205063
Highly Cited.
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
Christina Twyman-Saint Victor, Andrew J Rech, +22 authors, Andy J Minn.
Nature, 2015 Mar 11; 520(7547). PMID: 25754329    Free PMC article.
Highly Cited.
The PD-1 pathway in tolerance and autoimmunity.
Loise M Francisco, Peter T Sage, Arlene H Sharpe.
Immunol Rev, 2010 Jul 20; 236. PMID: 20636820    Free PMC article.
Highly Cited. Review.
Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade.
Rikke B Holmgaard, David A Schaer, +14 authors, Kyla E Driscoll.
J Immunother Cancer, 2018 Jun 06; 6(1). PMID: 29866156    Free PMC article.
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
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Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression.
Yisong Y Wan, Richard A Flavell.
Nature, 2007 Jan 16; 445(7129). PMID: 17220876
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FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis.
Rony Dahan, Emanuela Sega, +3 authors, Jeffrey V Ravetch.
Cancer Cell, 2015 Sep 17; 28(3). PMID: 26373277
Highly Cited.
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
Michel DuPage, Gaurav Chopra, +7 authors, Jeffrey A Bluestone.
Immunity, 2015 Feb 15; 42(2). PMID: 25680271    Free PMC article.
Highly Cited.
Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.
Bin Shang, Yao Liu, Shu-juan Jiang, Yi Liu.
Sci Rep, 2015 Oct 16; 5. PMID: 26462617    Free PMC article.
Highly Cited. Systematic Review.
CD73 expression on effector T cells sustained by TGF-β facilitates tumor resistance to anti-4-1BB/CD137 therapy.
Siqi Chen, Jie Fan, +10 authors, Bin Zhang.
Nat Commun, 2019 Jan 13; 10(1). PMID: 30635578    Free PMC article.
VISTA is an acidic pH-selective ligand for PSGL-1.
Robert J Johnston, Linhui Julie Su, +33 authors, Alan J Korman.
Nature, 2019 Oct 28; 574(7779). PMID: 31645726
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Stephan Herbertz, J Scott Sawyer, +9 authors, Michael M Lahn.
Drug Des Devel Ther, 2015 Aug 27; 9. PMID: 26309397    Free PMC article.
Highly Cited. Review.
Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection.
Neil J Shah, Ghassan Al-Shbool, +8 authors, Chul Kim.
J Immunother Cancer, 2019 Dec 19; 7(1). PMID: 31847881    Free PMC article.
Activation of NKT Cells in an Anti-PD-1-Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells.
Eun-Ah Bae, Hyungseok Seo, +10 authors, Chang-Yuil Kang.
Cancer Res, 2018 Jul 18; 78(18). PMID: 30012672
Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade.
Imran G House, Peter Savas, +17 authors, Paul A Beavis.
Clin Cancer Res, 2019 Oct 23; 26(2). PMID: 31636098
In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.
Sean P Arlauckas, Christopher S Garris, +9 authors, Mikael J Pittet.
Sci Transl Med, 2017 May 12; 9(389). PMID: 28490665    Free PMC article.
Highly Cited.
Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model.
Nadia M Luheshi, Jane Coates-Ulrichsen, +8 authors, Robert W Wilkinson.
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Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.
Marie Vétizou, Jonathan M Pitt, +35 authors, Laurence Zitvogel.
Science, 2015 Nov 07; 350(6264). PMID: 26541610    Free PMC article.
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
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Myeloid-derived suppressor cells coming of age.
Filippo Veglia, Michela Perego, Dmitry Gabrilovich.
Nat Immunol, 2018 Jan 20; 19(2). PMID: 29348500    Free PMC article.
Highly Cited. Review.
Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy.
Stephen Mok, Richard C Koya, +7 authors, Antoni Ribas.
Cancer Res, 2013 Nov 20; 74(1). PMID: 24247719    Free PMC article.
Highly Cited.
A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes.
Nisit Khandelwal, Marco Breinig, +13 authors, Philipp Beckhove.
EMBO Mol Med, 2015 Feb 19; 7(4). PMID: 25691366    Free PMC article.
A conserved dendritic-cell regulatory program limits antitumour immunity.
Barbara Maier, Andrew M Leader, +20 authors, Miriam Merad.
Nature, 2020 Apr 10; 580(7802). PMID: 32269339    Free PMC article.
Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model.
Raffaella Iannone, Lucio Miele, +2 authors, Silvana Morello.
Am J Cancer Res, 2014 Mar 25; 4(2). PMID: 24660106    Free PMC article.
Mouse and human iNKT cell agonist β-mannosylceramide reveals a distinct mechanism of tumor immunity.
Jessica J O'Konek, Petr Illarionov, +11 authors, Masaki Terabe.
J Clin Invest, 2011 Jan 20; 121(2). PMID: 21245578    Free PMC article.
Dynamics of the immune reaction to pancreatic cancer from inception to invasion.
Carolyn E Clark, Sunil R Hingorani, +3 authors, Robert H Vonderheide.
Cancer Res, 2007 Oct 03; 67(19). PMID: 17909062
Highly Cited.
TIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer.
Kaori Sakuishi, Shin Foong Ngiow, +4 authors, Ana C Anderson.
Oncoimmunology, 2013 Jun 05; 2(4). PMID: 23734331    Free PMC article.
Highly Cited.
Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.
Brian Ruffell, Debbie Chang-Strachan, +7 authors, Lisa M Coussens.
Cancer Cell, 2014 Dec 03; 26(5). PMID: 25446896    Free PMC article.
Highly Cited.
Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4.
Rikke B Holmgaard, Dmitriy Zamarin, +2 authors, James P Allison.
J Exp Med, 2013 Jun 12; 210(7). PMID: 23752227    Free PMC article.
Highly Cited.
CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade.
Limo Chen, Lixia Diao, +36 authors, Don L Gibbons.
Cancer Discov, 2018 Jul 18; 8(9). PMID: 30012853    Free PMC article.
Highly Cited.
The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy.
Arabella Young, Zoe Quandt, Jeffrey A Bluestone.
Cancer Immunol Res, 2018 Dec 05; 6(12). PMID: 30510057    Free PMC article.
Review.
The biology and functional importance of MAIT cells.
Dale I Godfrey, Hui-Fern Koay, James McCluskey, Nicholas A Gherardin.
Nat Immunol, 2019 Aug 14; 20(9). PMID: 31406380
Highly Cited. Review.
Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.
Hélène Salmon, Juliana Idoyaga, +19 authors, Miriam Merad.
Immunity, 2016 Apr 21; 44(4). PMID: 27096321    Free PMC article.
Highly Cited.
Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape.
Constance J Martin, Abhishek Datta, +19 authors, Thomas Schürpf.
Sci Transl Med, 2020 Mar 28; 12(536). PMID: 32213632
Tumor cell-intrinsic EPHA2 suppresses anti-tumor immunity by regulating PTGS2 (COX-2).
Nune Markosyan, Jinyang Li, +13 authors, Robert H Vonderheide.
J Clin Invest, 2019 Jun 05; 129(9). PMID: 31162144    Free PMC article.
Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans.
Daisuke Sugiyama, Hiroyoshi Nishikawa, +10 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2013 Oct 16; 110(44). PMID: 24127572    Free PMC article.
Highly Cited.
Macrophage biology in development, homeostasis and disease.
Thomas A Wynn, Ajay Chawla, Jeffrey W Pollard.
Nature, 2013 Apr 27; 496(7446). PMID: 23619691    Free PMC article.
Highly Cited. Review.
Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study.
Hans J Hammers, Elizabeth R Plimack, +12 authors, Asim Amin.
J Clin Oncol, 2017 Jul 06; 35(34). PMID: 28678668    Free PMC article.
Highly Cited.
Unconventional T Cell Targets for Cancer Immunotherapy.
Dale I Godfrey, Jérôme Le Nours, +2 authors, Jamie Rossjohn.
Immunity, 2018 Mar 22; 48(3). PMID: 29562195
Highly Cited. Review.
Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy.
Sangeeta Goswami, Irina Apostolou, +10 authors, Padmanee Sharma.
J Clin Invest, 2018 Jun 16; 128(9). PMID: 29905573    Free PMC article.
Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients.
Luciane Zabijak, Christophe Attencourt, +4 authors, Emmanuel Treiner.
Cancer Immunol Immunother, 2015 Oct 27; 64(12). PMID: 26497850
Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells.
Yulong Gao, Fernando Souza-Fonseca-Guimaraes, +21 authors, Mark J Smyth.
Nat Immunol, 2017 Aug 02; 18(9). PMID: 28759001
Highly Cited.
Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity.
David G DeNardo, Pauline Andreu, Lisa M Coussens.
Cancer Metastasis Rev, 2010 Apr 21; 29(2). PMID: 20405169    Free PMC article.
Highly Cited. Review.
MAIT Cells Promote Tumor Initiation, Growth, and Metastases via Tumor MR1.
Juming Yan, Stacey Allen, +10 authors, Michele W L Teng.
Cancer Discov, 2019 Dec 13; 10(1). PMID: 31826876
Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity.
Abigail E Overacre-Delgoffe, Maria Chikina, +15 authors, Dario A A Vignali.
Cell, 2017 May 30; 169(6). PMID: 28552348    Free PMC article.
Highly Cited.
Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy.
Shuhong Qi, Hui Li, +7 authors, Zhihong Zhang.
Elife, 2016 Nov 20; 5. PMID: 27855783    Free PMC article.
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
Anne Månsson Kvarnhammar, Niina Veitonmäki, +16 authors, Peter Ellmark.
J Immunother Cancer, 2019 Apr 13; 7(1). PMID: 30975201    Free PMC article.
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers.
Aaron M Goodman, Shumei Kato, +6 authors, Razelle Kurzrock.
Mol Cancer Ther, 2017 Aug 25; 16(11). PMID: 28835386    Free PMC article.
Highly Cited.
Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma.
Adil I Daud, Kimberly Loo, +15 authors, Michael D Rosenblum.
J Clin Invest, 2016 Aug 16; 126(9). PMID: 27525433    Free PMC article.
Highly Cited.
T-cell activation by transitory neo-antigens derived from distinct microbial pathways.
Alexandra J Corbett, Sidonia B G Eckle, +15 authors, James McCluskey.
Nature, 2014 Apr 04; 509(7500). PMID: 24695216
Highly Cited.
CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.
T Kawano, J Cui, +9 authors, M Taniguchi.
Science, 1997 Dec 31; 278(5343). PMID: 9374463
Highly Cited.
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.
Thibault Voron, Orianne Colussi, +15 authors, Magali Terme.
J Exp Med, 2015 Jan 21; 212(2). PMID: 25601652    Free PMC article.
Highly Cited.
Severe gastrointestinal toxicity with administration of trametinib in combination with dabrafenib and ipilimumab.
David R Minor, Igor Puzanov, +2 authors, Axel Hoos.
Pigment Cell Melanoma Res, 2015 May 23; 28(5). PMID: 25996827    Free PMC article.
Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.
Ashanty M Melo, Aisling M O'Brien, +15 authors, Margaret R Dunne.
Front Immunol, 2019 Jul 30; 10. PMID: 31354725    Free PMC article.
Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment.
Stefani Spranger, Holly K Koblish, +3 authors, Thomas F Gajewski.
J Immunother Cancer, 2014 May 16; 2. PMID: 24829760    Free PMC article.
Highly Cited.
High-Throughput Screening of Combinatorial Immunotherapies with Patient-Specific In Silico Models of Metastatic Colorectal Cancer.
Jakob Nikolas Kather, Pornpimol Charoentong, +9 authors, Niels Halama.
Cancer Res, 2018 Jul 04; 78(17). PMID: 29967263
Assessing Immune-Related Adverse Events of Efficacious Combination Immunotherapies in Preclinical Models of Cancer.
Jing Liu, Stephen J Blake, +7 authors, Michele W L Teng.
Cancer Res, 2016 Aug 10; 76(18). PMID: 27503925
Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.
David Wang, Jason Quiros, +12 authors, Michel DuPage.
Cell Rep, 2018 Jun 14; 23(11). PMID: 29898397    Free PMC article.
Highly Cited.
A2AR Adenosine Signaling Suppresses Natural Killer Cell Maturation in the Tumor Microenvironment.
Arabella Young, Shin Foong Ngiow, +14 authors, Mark J Smyth.
Cancer Res, 2017 Dec 13; 78(4). PMID: 29229601
Highly Cited.
Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses.
Kelly D Moynihan, Cary F Opel, +19 authors, Darrell J Irvine.
Nat Med, 2016 Nov 01; 22(12). PMID: 27775706    Free PMC article.
Highly Cited.
The regulatory role of invariant NKT cells in tumor immunity.
Rosanna M McEwen-Smith, Mariolina Salio, Vincenzo Cerundolo.
Cancer Immunol Res, 2015 May 06; 3(5). PMID: 25941354    Free PMC article.
Highly Cited. Review.
Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity.
Santiago Zelenay, Annemarthe G van der Veen, +9 authors, Caetano Reis e Sousa.
Cell, 2015 Sep 08; 162(6). PMID: 26343581    Free PMC article.
Highly Cited.
Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo.
Mei-Ling Chen, Mikaël J Pittet, +4 authors, Khashayarsha Khazaie.
Proc Natl Acad Sci U S A, 2004 Dec 30; 102(2). PMID: 15623559    Free PMC article.
Highly Cited.
MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets.
A Kurioka, J E Ussher, +8 authors, P Klenerman.
Mucosal Immunol, 2014 Oct 02; 8(2). PMID: 25269706    Free PMC article.
Highly Cited.
Taming the Sentinels: Microbiome-Derived Metabolites and Polarization of T Cells.
Lukasz Wojciech, Kevin S W Tan, Nicholas R J Gascoigne.
Int J Mol Sci, 2020 Oct 23; 21(20). PMID: 33086747    Free PMC article.
Review.
The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression.
Federica Caponnetto, Emiliano Dalla, +8 authors, Daniela Cesselli.
Biomedicines, 2020 Dec 09; 8(12). PMID: 33287106    Free PMC article.
Exploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy.
Qin Qiu, Yuqi Lin, +8 authors, Lianxiang Luo.
Front Immunol, 2021 Jan 26; 11. PMID: 33488618    Free PMC article.
Review.
Inflammation-Driven Breast Tumor Cell Plasticity: Stemness/EMT, Therapy Resistance and Dormancy.
Tamir Baram, Linor Rubinstein-Achiasaf, Hagar Ben-Yaakov, Adit Ben-Baruch.
Front Oncol, 2021 Feb 16; 10. PMID: 33585241    Free PMC article.
Review.
Identification of a ceRNA Network in Lung Adenocarcinoma Based on Integration Analysis of Tumor-Associated Macrophage Signature Genes.
Lei Zhang, Kai Zhang, +7 authors, Jiaxiang Wang.
Front Cell Dev Biol, 2021 Mar 20; 9. PMID: 33738286    Free PMC article.
Leveraging NKG2D Ligands in Immuno-Oncology.
Mercedes Beatriz Fuertes, Carolina Inés Domaica, Norberto Walter Zwirner.
Front Immunol, 2021 Aug 17; 12. PMID: 34394116    Free PMC article.
Review.
PD-1-stimulated T cell subsets are transcriptionally and functionally distinct.
Shalom Lerrer, Anna S Tocheva, +2 authors, Adam Mor.
iScience, 2021 Sep 16; 24(9). PMID: 34522863    Free PMC article.
Improving function of cytotoxic T-lymphocytes by transforming growth factor-β inhibitor in oral squamous cell carcinoma.
Yutaro Kondo, Susumu Suzuki, +11 authors, Toru Nagao.
Cancer Sci, 2021 Jul 27; 112(10). PMID: 34309966    Free PMC article.
Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma.
Mark A Exley, Samantha Garcia, +2 authors, David W Andrews.
J Clin Med, 2022 Feb 26; 11(4). PMID: 35207340    Free PMC article.
Review.
Discovery and pharmacological characterization of cetrelimab (JNJ-63723283), an anti-programmed cell death protein-1 (PD-1) antibody, in human cancer models.
Nikki DeAngelis, Catherine Ferrante, +13 authors, Raluca I Verona.
Cancer Chemother Pharmacol, 2022 Mar 18; 89(4). PMID: 35298699    Free PMC article.
Polarization of tumor-associated macrophages by TLR7/8 conjugated radiosensitive peptide hydrogel for overcoming tumor radioresistance.
Yumin Zhang, Zujian Feng, +6 authors, Jianfeng Liu.
Bioact Mater, 2022 Apr 08; 16. PMID: 35386314    Free PMC article.