Review
. 2021 Dec; 9(12):.
doi: 10.3390/vaccines9121392.

Directing T-Cell Immune Responses for Cancer Vaccination and Immunotherapy

Peter Lawrence Smith 1 Katarzyna Piadel 1 Angus George Dalgleish 1 
Affiliations
  • PMID: 34960140
  •     239 References
  •     1 citations

Abstract

Cancer vaccination and immunotherapy revolutionised the treatment of cancer, a result of decades of research into the immune system in health and disease. However, despite recent breakthroughs in treating otherwise terminal cancer, only a minority of patients respond to cancer immunotherapy and some cancers are largely refractive to immunotherapy treatment. This is due to numerous issues intrinsic to the tumour, its microenvironment, or the immune system. CD4+ and CD8+ αβ T-cells emerged as the primary effector cells of the anti-tumour immune response but their function in cancer patients is often compromised. This review details the mechanisms by which T-cell responses are hindered in the setting of cancer and refractive to immunotherapy, and details many of the approaches under investigation to direct T-cell function and improve the efficacy of cancer vaccination and immunotherapy.

Keywords: T-cell; cancer; checkpoint inhibition; immunotherapy; metabolism; microbiome; vaccine.

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Deletion of PTPN22 improves effector and memory CD8+ T cell responses to tumors.
Rebecca J Brownlie, David Wright, Rose Zamoyska, Robert J Salmond.
JCI Insight, 2019 Jul 25; 5. PMID: 31335326    Free PMC article.
Targeting immune dysfunction in aging.
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Ageing Res Rev, 2021 Jul 20; 70. PMID: 34280555
Review.
Dietary Fiber Confers Protection against Flu by Shaping Ly6c- Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism.
Aurélien Trompette, Eva S Gollwitzer, +7 authors, Benjamin J Marsland.
Immunity, 2018 May 17; 48(5). PMID: 29768180
Highly Cited.
Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway.
J Park, M Kim, +4 authors, C H Kim.
Mucosal Immunol, 2014 Jun 12; 8(1). PMID: 24917457    Free PMC article.
Highly Cited.
Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function.
Andrea Boni, Alexandria P Cogdill, +9 authors, Jennifer A Wargo.
Cancer Res, 2010 Jun 17; 70(13). PMID: 20551059
Highly Cited.
Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs.
Lei Lu, Xiaobing Xu, +3 authors, Xuan Wang.
J Transl Med, 2014 Feb 08; 12. PMID: 24502656    Free PMC article.
Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors.
Bonnie S Glisson, Rom S Leidner, +13 authors, Sandip Pravin Patel.
Clin Cancer Res, 2020 Aug 21; 26(20). PMID: 32816951
Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion.
Yi-Ru Yu, Hana Imrichova, +17 authors, Ping-Chih Ho.
Nat Immunol, 2020 Oct 07; 21(12). PMID: 33020660
Radiation therapy and anti-tumor immunity: exposing immunogenic mutations to the immune system.
Claire Lhuillier, Nils-Petter Rudqvist, +2 authors, Sandra Demaria.
Genome Med, 2019 Jun 22; 11(1). PMID: 31221199    Free PMC article.
Highly Cited. Review.
Autologous tumor vaccine modified with recombinant new castle disease virus expressing IL-7 promotes antitumor immune response.
Lixiang Zhao, Yu Mei, +6 authors, Haiyan Liu.
J Immunol, 2014 Jun 20; 193(2). PMID: 24943214
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.
David J Messenheimer, Shawn M Jensen, +6 authors, Bernard A Fox.
Clin Cancer Res, 2017 Sep 01; 23(20). PMID: 28855348    Free PMC article.
Highly Cited.
Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model.
Shihao Chen, Li-Fen Lee, +12 authors, John C Lin.
Cancer Immunol Res, 2014 Nov 13; 3(2). PMID: 25387892
Highly Cited.
Retinoic acid as a vaccine adjuvant enhances CD8+ T cell response and mucosal protection from viral challenge.
Xuefang Tan, Jamie L Sande, +2 authors, Philip D Greenberg.
J Virol, 2011 Jun 10; 85(16). PMID: 21653670    Free PMC article.
AMPK: a nutrient and energy sensor that maintains energy homeostasis.
D Grahame Hardie, Fiona A Ross, Simon A Hawley.
Nat Rev Mol Cell Biol, 2012 Mar 23; 13(4). PMID: 22436748    Free PMC article.
Highly Cited. Review.
Vitamin D and human health: lessons from vitamin D receptor null mice.
Roger Bouillon, Geert Carmeliet, +6 authors, Marie Demay.
Endocr Rev, 2008 Aug 13; 29(6). PMID: 18694980    Free PMC article.
Highly Cited. Review.
Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Chrysothemis C Brown, Daria Esterhazy, +11 authors, Randolph J Noelle.
Immunity, 2015 Mar 15; 42(3). PMID: 25769610    Free PMC article.
Highly Cited.
IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade.
Valérie Ostiguy, Eve-Line Allard, +2 authors, Nathalie Labrecque.
J Leukoc Biol, 2007 Jun 08; 82(3). PMID: 17554014
Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming.
Dominic G Roy, Jocelyn Chen, +23 authors, Russell G Jones.
Cell Metab, 2020 Feb 06; 31(2). PMID: 32023446
The small molecule TGF-β signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis.
Kendra Garrison, Tobias Hahn, +3 authors, Emmanuel T Akporiaye.
Cancer Immunol Immunother, 2011 Oct 06; 61(4). PMID: 21971588    Free PMC article.
Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity.
Olga Kogkopoulou, Evaggelos Tzakos, +4 authors, George Thyphronitis.
J Leukoc Biol, 2006 Feb 16; 79(5). PMID: 16478922
Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability.
Maurizio Rossini, Susanna Maddali Bongi, +7 authors, Silvano Adami.
Arthritis Res Ther, 2010 Dec 01; 12(6). PMID: 21114806    Free PMC article.
Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.
Manisha Singh, Christina Vianden, +15 authors, Willem W Overwijk.
Nat Commun, 2017 Nov 14; 8(1). PMID: 29129918    Free PMC article.
When Aging Reaches CD4+ T-Cells: Phenotypic and Functional Changes.
Marco Antonio Moro-García, Rebeca Alonso-Arias, Carlos López-Larrea.
Front Immunol, 2013 May 16; 4. PMID: 23675374    Free PMC article.
Epidemic influenza and vitamin D.
J J Cannell, R Vieth, +5 authors, E Giovannucci.
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Highly Cited. Review.
Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy.
Ying Li, Yanni Cong, +10 authors, Shengdian Wang.
Nat Commun, 2021 Feb 13; 12(1). PMID: 33574265    Free PMC article.
Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients.
Ilaria Grazia Zizzari, Alessandra Di Filippo, +12 authors, Chiara Napoletano.
J Pers Med, 2020 Nov 08; 10(4). PMID: 33158018    Free PMC article.
PI3Kδ coordinates transcriptional, chromatin, and metabolic changes to promote effector CD8+ T cells at the expense of central memory.
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Cell Rep, 2021 Oct 14; 37(2). PMID: 34644563    Free PMC article.
The p38 Pathway: From Biology to Cancer Therapy.
Adrián Martínez-Limón, Manel Joaquin, +2 authors, Eulàlia de Nadal.
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Nat Immunol, 2019 Jul 31; 20(9). PMID: 31358999    Free PMC article.
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Targeting the MAPK and PI3K pathways in combination with PD1 blockade in melanoma.
Marcel A Deken, Jules Gadiot, +13 authors, Christian U Blank.
Oncoimmunology, 2017 Jan 27; 5(12). PMID: 28123875    Free PMC article.
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Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma.
Heather L Thompson, Megan J Smithey, Charles D Surh, Janko Nikolich-Žugich.
Front Immunol, 2017 Jul 01; 8. PMID: 28659930    Free PMC article.
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A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors.
Jeffrey S Miller, Chihiro Morishima, +12 authors, Kevin C Conlon.
Clin Cancer Res, 2017 Dec 06; 24(7). PMID: 29203590    Free PMC article.
Systemic Immune-Inflammation Index and Changes of Neutrophil-Lymphocyte Ratio as Prognostic Biomarkers for Patients With Pancreatic Cancer Treated With Immune Checkpoint Blockade.
Jin Shang, Xiao Han, +7 authors, Yi Hu.
Front Oncol, 2021 Mar 16; 11. PMID: 33718140    Free PMC article.
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Clin Cancer Res, 2020 Dec 24; 27(7). PMID: 33355238    Free PMC article.
The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.
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Science, 2018 Jan 06; 359(6371). PMID: 29302014    Free PMC article.
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L-arginine reduces mitochondrial dysfunction and airway injury in murine allergic airway inflammation.
Ulaganathan Mabalirajan, Tanveer Ahmad, +3 authors, Balaram Ghosh.
Int Immunopharmacol, 2010 Sep 16; 10(12). PMID: 20840838
Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma.
Dmitriy Timerman, Melissa McEnery-Stonelake, +5 authors, Jennifer Y Lin.
Oncotarget, 2016 Dec 31; 8(4). PMID: 28036288    Free PMC article.
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Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis.
Andrea Schietinger, Mary Philip, +10 authors, Philip D Greenberg.
Immunity, 2016 Aug 16; 45(2). PMID: 27521269    Free PMC article.
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An intra-tumoral niche maintains and differentiates stem-like CD8 T cells.
Caroline S Jansen, Nataliya Prokhnevska, +26 authors, Haydn Kissick.
Nature, 2019 Dec 13; 576(7787). PMID: 31827286    Free PMC article.
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Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming.
Michael D Buck, David O'Sullivan, +16 authors, Erika L Pearce.
Cell, 2016 Jun 14; 166(1). PMID: 27293185    Free PMC article.
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TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells.
Hayato Takahashi, Tomohiko Kanno, +8 authors, John J O'Shea.
Nat Immunol, 2012 May 01; 13(6). PMID: 22544395    Free PMC article.
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The effect of concomitant use of statins, NSAIDs, low-dose aspirin, metformin and beta-blockers on outcomes in patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.
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Systematic Review.
Non-Provitamin A and Provitamin A Carotenoids as Immunomodulators: Recommended Dietary Allowance, Therapeutic Index, or Personalized Nutrition?
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Oxid Med Cell Longev, 2018 Jun 05; 2018. PMID: 29861829    Free PMC article.
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Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
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Science, 2015 Nov 07; 350(6264). PMID: 26541606    Free PMC article.
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The p38 MAPK Inhibitor SB203580 Abrogates Tumor Necrosis Factor-Induced Proliferative Expansion of Mouse CD4+Foxp3+ Regulatory T Cells.
Tianzhen He, Shuoyang Liu, +4 authors, Xin Chen.
Front Immunol, 2018 Jul 25; 9. PMID: 30038619    Free PMC article.
Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity.
Alexey Berezhnoy, Iris Castro, +2 authors, Eli Gilboa.
J Clin Invest, 2013 Dec 03; 124(1). PMID: 24292708    Free PMC article.
High-Dose Nicotinamide Suppresses ROS Generation and Augments Population Expansion during CD8(+) T Cell Activation.
Ho Jin Choi, So-Young Jang, Eun Seong Hwang.
Mol Cells, 2015 Oct 08; 38(10). PMID: 26442863    Free PMC article.
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Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.
Diwakar Davar, Amiran K Dzutsev, +29 authors, Hassane M Zarour.
Science, 2021 Feb 06; 371(6529). PMID: 33542131    Free PMC article.
Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy.
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Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer.
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Clin Cancer Res, 2018 Mar 20; 24(8). PMID: 29549159
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Nat Rev Cancer, 2018 Apr 27; 18(7). PMID: 29695749
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Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D3-mediated effects.
A Takeuchi, G S Reddy, +3 authors, S Sharma.
J Immunol, 1998 Apr 29; 160(1). PMID: 9551973
Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription.
Marcos Vidal, Chilakamarti V Ramana, Adriana S Dusso.
Mol Cell Biol, 2002 Mar 23; 22(8). PMID: 11909970    Free PMC article.
Cutting Edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right.
Carl E Ruby, Melissa A Yates, +5 authors, Andrew D Weinberg.
J Immunol, 2009 Sep 30; 183(8). PMID: 19786544    Free PMC article.
Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade.
Gladys Ferrere, Maryam Tidjani Alou, +25 authors, Laurence Zitvogel.
JCI Insight, 2020 Dec 16; 6(2). PMID: 33320838    Free PMC article.
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Retinoic Acid and Immune Homeostasis: A Balancing Act.
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Trends Immunol, 2017 Jan 18; 38(3). PMID: 28094101
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Enhancing CD8 T-cell memory by modulating fatty acid metabolism.
Erika L Pearce, Matthew C Walsh, +5 authors, Yongwon Choi.
Nature, 2009 Jun 06; 460(7251). PMID: 19494812    Free PMC article.
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Methionine restriction leads to hyperhomocysteinemia and alters hepatic H2S production capacity in Fischer-344 rats.
Nahid Tamanna, Shyamchand Mayengbam, James D House, Jason R Treberg.
Mech Ageing Dev, 2018 Oct 28; 176. PMID: 30367932
Chronic viral infections impinge on naive bystander CD8 T cells.
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Immun Inflamm Dis, 2020 Mar 29; 8(3). PMID: 32220007    Free PMC article.
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Highly Cited. Review.
Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior.
Michio Miyajima, Baihao Zhang, +18 authors, Sidonia Fagarasan.
Nat Immunol, 2017 Oct 24; 18(12). PMID: 29058703
Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent.
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J Clin Invest, 2020 May 29; 130(9). PMID: 32463803    Free PMC article.
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Science, 2019 Nov 09; 366(6468). PMID: 31699883    Free PMC article.
Highly Cited.
OX40 is a potent immune-stimulating target in late-stage cancer patients.
Brendan D Curti, Magdalena Kovacsovics-Bankowski, +20 authors, Andrew D Weinberg.
Cancer Res, 2013 Nov 02; 73(24). PMID: 24177180    Free PMC article.
Highly Cited.
Mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2-dependent pathways are essential for CD8+ T cell-mediated airway hyperresponsiveness and inflammation.
Hiroshi Ohnishi, Katsuyuki Takeda, +5 authors, Erwin W Gelfand.
J Allergy Clin Immunol, 2009 Jan 10; 123(1). PMID: 19130938
CD3ζ-chain expression of human T lymphocytes is regulated by TNF via Src-like adaptor protein-dependent proteasomal degradation.
Barbara Érsek, Viktor Molnár, +5 authors, György Nagy.
J Immunol, 2012 Jul 17; 189(4). PMID: 22798681
The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.
Sophie Viaud, Fabiana Saccheri, +30 authors, Laurence Zitvogel.
Science, 2013 Nov 23; 342(6161). PMID: 24264990    Free PMC article.
Highly Cited.
Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies.
Marc Pellegrini, Thomas Calzascia, +12 authors, Tak W Mak.
Nat Med, 2009 Apr 28; 15(5). PMID: 19396174
Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.
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Cancer Cell, 2020 Jun 10; 37(6). PMID: 32516591
Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma.
Erik Ladomersky, Lijie Zhai, +22 authors, Derek A Wainwright.
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Chronic virus infection compromises memory bystander T cell function in an IL-6/STAT1-dependent manner.
Isabel Barnstorf, Mariana Borsa, +7 authors, Annette Oxenius.
J Exp Med, 2019 Feb 13; 216(3). PMID: 30745322    Free PMC article.
Microbial pathways in colonic sulfur metabolism and links with health and disease.
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Front Physiol, 2012 Dec 12; 3. PMID: 23226130    Free PMC article.
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Cristina Ferreira, Leandro Barros, +11 authors, Marc Veldhoen.
Nat Immunol, 2020 May 20; 21(7). PMID: 32424367
Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals.
A Murayama, K Takeyama, +4 authors, S Kato.
Endocrinology, 1999 Apr 28; 140(5). PMID: 10218975
Lessons to Learn From Low-Dose Cyclosporin-A: A New Approach for Unexpected Clinical Applications.
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Front Immunol, 2019 Apr 16; 10. PMID: 30984176    Free PMC article.
Review.
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Highly Cited. Review.
T Cell Dysfunction and Exhaustion in Cancer.
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Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02).
Adi Diab, Nizar M Tannir, +20 authors, Daniel C Cho.
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Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System.
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Annu Rev Immunol, 2016 May 12; 34. PMID: 27168242
Highly Cited. Review.
Immunosenescence: a key player in cancer development.
Jingyao Lian, Ying Yue, Weina Yu, Yi Zhang.
J Hematol Oncol, 2020 Nov 11; 13(1). PMID: 33168037    Free PMC article.
Review.
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Juan Feng, Silin Lü, +2 authors, Xian Wang.
Protein Cell, 2016 Feb 10; 7(6). PMID: 26856873    Free PMC article.
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Nature, 2016 Mar 17; 531(7596). PMID: 26982734    Free PMC article.
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First-in-human phase 1 study of MK-1248, an anti-glucocorticoid-induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors.
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Cancer, 2020 Aug 19; 126(22). PMID: 32809217
IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity.
Guoliang Cui, Matthew M Staron, +4 authors, Susan M Kaech.
Cell, 2015 May 11; 161(4). PMID: 25957683    Free PMC article.
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Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth.
Alastair M McKee, Benjamin M Kirkup, +22 authors, Stephen D Robinson.
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Metformin Enhances the Antitumor Activity of CD8+ T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway.
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J Immunol, 2020 Mar 30; 204(9). PMID: 32221038
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages.
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Immunity, 2019 Jan 27; 50(2). PMID: 30683619    Free PMC article.
Highly Cited.
Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer.
Shi-Long Zhang, Yu-Qin Mao, +7 authors, Li-Shun Wang.
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Highly Cited.
GEN-1 immunotherapy for the treatment of ovarian cancer.
Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer.
Future Oncol, 2018 Oct 17; 15(4). PMID: 30325199
Review.
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors.
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Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation.
Adam D Cohen, David A Schaer, +10 authors, Jedd D Wolchok.
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Autophagy is essential for effector CD8(+) T cell survival and memory formation.
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Nat Immunol, 2014 Nov 05; 15(12). PMID: 25362489    Free PMC article.
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Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes.
Ristan M Greer, Sharon L Portelli, +4 authors, Louise S Conwell.
Pediatr Diabetes, 2012 Aug 24; 14(1). PMID: 22913562
Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.
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Highly Cited.
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy.
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Immune regulation by microbiome metabolites.
Chang H Kim.
Immunology, 2018 Mar 24; 154(2). PMID: 29569377    Free PMC article.
Highly Cited. Review.
Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8+ T Cells.
Annabell Bachem, Christina Makhlouf, +22 authors, Sammy Bedoui.
Immunity, 2019 Jul 06; 51(2). PMID: 31272808
Highly Cited.
IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors.
Michael J Allegrezza, Melanie R Rutkowski, +11 authors, Jose R Conejo-Garcia.
Cancer Res, 2016 Mar 17; 76(9). PMID: 26980764    Free PMC article.
CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help.
R R French, H T Chan, A L Tutt, M J Glennie.
Nat Med, 1999 May 06; 5(5). PMID: 10229232
Highly Cited.
Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes.
Lutfan Lazuardi, Brigitte Jenewein, +3 authors, Beatrix Grubeck-Loebenstein.
Immunology, 2004 Dec 21; 114(1). PMID: 15606793    Free PMC article.
Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.
Rong Zeng, Rosanne Spolski, +9 authors, Warren J Leonard.
J Exp Med, 2005 Jan 05; 201(1). PMID: 15630141    Free PMC article.
Highly Cited.
Memory T cells: strategies for optimizing tumor immunotherapy.
Qingjun Liu, Zhongjie Sun, Ligong Chen.
Protein Cell, 2020 Mar 30; 11(8). PMID: 32221812    Free PMC article.
Review.
The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction.
Nicole E Scharping, Ashley V Menk, +5 authors, Greg M Delgoffe.
Immunity, 2016 Aug 09; 45(2). PMID: 27496732    Free PMC article.
Highly Cited.
Normalizing Microbiota-Induced Retinoic Acid Deficiency Stimulates Protective CD8(+) T Cell-Mediated Immunity in Colorectal Cancer.
Nupur Bhattacharya, Robert Yuan, +14 authors, Edgar G Engleman.
Immunity, 2016 Sep 04; 45(3). PMID: 27590114    Free PMC article.
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.
Kristen E Pauken, Morgan A Sammons, +16 authors, E John Wherry.
Science, 2016 Oct 30; 354(6316). PMID: 27789795    Free PMC article.
Highly Cited.
Autoimmunity linked protein phosphatase PTPN22 as a target for cancer immunotherapy.
Rafael Cubas, Zia Khan, +7 authors, Andrew C Chan.
J Immunother Cancer, 2020 Nov 01; 8(2). PMID: 33127657    Free PMC article.
Activation of p38 mitogen-activated protein kinase is critical step for acquisition of effector function in cytokine-activated T cells, but acts as a negative regulator in T cells activated through the T-cell receptor.
Ching Li, Paul Beavis, +3 authors, Fionula M Brennan.
Immunology, 2010 Sep 30; 132(1). PMID: 20875074    Free PMC article.
Interleukin-21 has activity in patients with metastatic melanoma: a phase II study.
Teresa M Petrella, Richard Tozer, +10 authors, Elizabeth A Eisenhauer.
J Clin Oncol, 2012 Aug 24; 30(27). PMID: 22915661
mTORC1 and mTORC2 selectively regulate CD8⁺ T cell differentiation.
Kristen N Pollizzi, Chirag H Patel, +5 authors, Jonathan D Powell.
J Clin Invest, 2015 Apr 22; 125(5). PMID: 25893604    Free PMC article.
Highly Cited.
Using CRISPR to enhance T cell effector function for therapeutic applications.
Julian J Freen-van Heeren.
Cytokine X, 2021 Feb 20; 3(1). PMID: 33604565    Free PMC article.
Review.
Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study.
David F McDermott, Jeffrey A Sosman, +11 authors, Thomas Powles.
J Clin Oncol, 2016 Jan 13; 34(8). PMID: 26755520
Highly Cited.
The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant.
Delphine L Lauté-Caly, Emma J Raftis, +7 authors, Imke E Mulder.
Sci Rep, 2019 Jan 30; 9(1). PMID: 30692549    Free PMC article.
Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC.
Kwan Ho Tang, Shuai Li, +15 authors, Benjamin G Neel.
Cancer Discov, 2021 Aug 07; 12(1). PMID: 34353854    Free PMC article.
ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients.
O Trédan, C Ménétrier-Caux, +21 authors, C Caux.
Ann Oncol, 2015 Apr 09; 26(7). PMID: 25851629
Cyp26b1 regulates retinoic acid-dependent signals in T cells and its expression is inhibited by transforming growth factor-β.
Hajime Takeuchi, Aya Yokota, Yoshiharu Ohoka, Makoto Iwata.
PLoS One, 2011 Jan 21; 6(1). PMID: 21249211    Free PMC article.
Variations in vitamin D production could possibly explain the seasonality of childhood respiratory infections in Hawaii.
William B Grant.
Pediatr Infect Dis J, 2008 Jul 23; 27(9). PMID: 18645543
Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists.
Christopher T Petersen, Mojibade Hassan, +9 authors, Edmund K Waller.
Blood Adv, 2018 Feb 02; 2(3). PMID: 29386194    Free PMC article.
Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction.
Tingting Wang, J N Rashida Gnanaprakasam, +20 authors, Ruoning Wang.
Nat Metab, 2020 Jul 23; 2(7). PMID: 32694789    Free PMC article.
Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab.
Jingjing Liu, Shuang Li, +7 authors, Ying Cheng.
J Clin Lab Anal, 2019 Jul 10; 33(8). PMID: 31282096    Free PMC article.
Highly Cited.
Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation.
Marcos P Damasio, Julia M Marchingo, +3 authors, Andrew J M Howden.
Biochem J, 2020 Dec 12; 478(1). PMID: 33305809    Free PMC article.
Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation.
Khashayar Esfahani, Tho-Alfakar Al-Aubodah, +9 authors, Wilson H Miller.
Nat Commun, 2019 Oct 19; 10(1). PMID: 31624262    Free PMC article.
Systemic immune-inflammation index, SII, for prognosis of elderly patients with newly diagnosed tumors.
Chan Li, Wei Tian, +5 authors, Ke Xie.
Oncotarget, 2018 Nov 20; 9(82). PMID: 30450158    Free PMC article.
Advances in the Immunomodulatory Properties of Glycoantigens in Cancer.
Valeria da Costa, Teresa Freire.
Cancers (Basel), 2022 Apr 24; 14(8). PMID: 35454762    Free PMC article.
Review.