Review
. 2021 Aug; 13(7):.
doi: 10.3390/pharmaceutics13071016.

The Role of Mathematical Models in Immuno-Oncology: Challenges and Future Perspectives

Aymara Sancho-Araiz 1 Victor Mangas-Sanjuan 2 Iñaki F Trocóniz 1 
Affiliations
  • PMID: 34371708
  •     99 References

Abstract

Immuno-oncology (IO) focuses on the ability of the immune system to detect and eliminate cancer cells. Since the approval of the first immune checkpoint inhibitor, immunotherapies have become a major player in oncology treatment and, in 2021, represented the highest number of approved drugs in the field. In spite of this, there is still a fraction of patients that do not respond to these therapies and develop resistance mechanisms. In this sense, mathematical models offer an opportunity to identify predictive biomarkers, optimal dosing schedules and rational combinations to maximize clinical response. This work aims to outline the main therapeutic targets in IO and to provide a description of the different mathematical approaches (top-down, middle-out, and bottom-up) integrating the cancer immunity cycle with immunotherapeutic agents in clinical scenarios. Among the different strategies, middle-out models, which combine both theoretical and evidence-based description of tumor growth and immunological cell-type dynamics, represent an optimal framework to evaluate new IO strategies.

Keywords: PK/PD; bottom-up approach; immuno-oncology; mathematical modeling; middle-out approach; top-down approach.

Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective.
Casey Quinn, Louis P Garrison, +8 authors, Elise Wu.
J Immunother Cancer, 2020 Jul 15; 8(2). PMID: 32661115    Free PMC article.
Mathematical model approach to describe tumour response in mice after vaccine administration and its applicability to immune-stimulatory cytokine-based strategies.
Zinnia P Parra-Guillen, Pedro Berraondo, +2 authors, Iñaki F Troconiz.
AAPS J, 2013 Apr 23; 15(3). PMID: 23605806    Free PMC article.
Toxicity and management in CAR T-cell therapy.
Challice L Bonifant, Hollie J Jackson, Renier J Brentjens, Kevin J Curran.
Mol Ther Oncolytics, 2016 Sep 15; 3. PMID: 27626062    Free PMC article.
Highly Cited. Review.
Differences in Tumor Immune Microenvironment in Metastatic Sites of Breast Cancer.
Hyunjong Lee, Kwon Joong Na, Hongyoon Choi.
Front Oncol, 2021 Apr 06; 11. PMID: 33816302    Free PMC article.
Computational modelling of modern cancer immunotherapy.
Damijan Valentinuzzi, Robert Jeraj.
Phys Med Biol, 2020 Oct 23; 65(24). PMID: 33091898
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
Shannon L Maude, Theodore W Laetsch, +32 authors, Stephan A Grupp.
N Engl J Med, 2018 Feb 01; 378(5). PMID: 29385370    Free PMC article.
Highly Cited.
VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy.
J Louise Lines, Lorenzo F Sempere, +2 authors, Randolph Noelle.
Cancer Immunol Res, 2014 Jun 05; 2(6). PMID: 24894088    Free PMC article.
Highly Cited.
Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model.
Huilin Ma, Hanwen Wang, +3 authors, Aleksander S Popel.
J Immunother Cancer, 2020 Aug 30; 8(2). PMID: 32859743    Free PMC article.
Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors.
Shin Foong Ngiow, Bianca von Scheidt, +3 authors, Mark J Smyth.
Cancer Res, 2011 Mar 25; 71(10). PMID: 21430066
Highly Cited.
B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK.
Andrew C Vendel, Jill Calemine-Fenaux, +3 authors, Dan L Eaton.
J Immunol, 2009 Jan 22; 182(3). PMID: 19155498
Anti-CTLA-4 immunotherapy: uncoupling toxicity and efficacy.
Jonathan Pol, Guido Kroemer.
Cell Res, 2018 Mar 30; 28(5). PMID: 29593340    Free PMC article.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Shawn D Blackburn, Haina Shin, +7 authors, E John Wherry.
Nat Immunol, 2008 Dec 02; 10(1). PMID: 19043418    Free PMC article.
Highly Cited.
CAR-T cells: the long and winding road to solid tumors.
Maria Michela D'Aloia, Ilaria Grazia Zizzari, +2 authors, Maurizio Alimandi.
Cell Death Dis, 2018 Feb 17; 9(3). PMID: 29449531    Free PMC article.
Highly Cited. Review.
Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.
Mark E Dudley, John R Wunderlich, +16 authors, Steven A Rosenberg.
Science, 2002 Sep 21; 298(5594). PMID: 12242449    Free PMC article.
Highly Cited.
A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma.
Andrea Wang-Gillam, Stacey Plambeck-Suess, +9 authors, Williams G Hawkins.
Invest New Drugs, 2012 Aug 07; 31(3). PMID: 22864469    Free PMC article.
Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes.
Claudia Cocco, Fabio Morandi, Irma Airoldi.
Cells, 2021 May 01; 10(4). PMID: 33920505    Free PMC article.
Review.
Immune checkpoint inhibitors: recent progress and potential biomarkers.
Pramod Darvin, Salman M Toor, Varun Sasidharan Nair, Eyad Elkord.
Exp Mol Med, 2018 Dec 14; 50(12). PMID: 30546008    Free PMC article.
Highly Cited. Review.
Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia.
Marco L Davila, Isabelle Riviere, +29 authors, Renier Brentjens.
Sci Transl Med, 2014 Feb 21; 6(224). PMID: 24553386    Free PMC article.
Highly Cited.
Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies.
Xinjie Xu, Qihang Sun, +8 authors, Yuhua Li.
Front Immunol, 2019 Dec 05; 10. PMID: 31798590    Free PMC article.
Review.
Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.
Y Kawakami, S Eliyahu, +7 authors, S A Rosenberg.
Proc Natl Acad Sci U S A, 1994 Jul 05; 91(14). PMID: 8022805    Free PMC article.
Highly Cited.
A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade.
Oleg Milberg, Chang Gong, +6 authors, Aleksander S Popel.
Sci Rep, 2019 Aug 04; 9(1). PMID: 31375756    Free PMC article.
A Computational Model of Neoadjuvant PD-1 Inhibition in Non-Small Cell Lung Cancer.
Mohammad Jafarnejad, Chang Gong, +6 authors, Aleksander S Popel.
AAPS J, 2019 Jun 27; 21(5). PMID: 31236847    Free PMC article.
CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies.
Hannah M Knochelmann, Aubrey S Smith, +3 authors, Chrystal M Paulos.
Front Immunol, 2018 Aug 25; 9. PMID: 30140266    Free PMC article.
Highly Cited. Review.
Chimeric Antigen Receptor T Cells in Hematologic Malignancies.
Brandon R Shank, Bryan Do, +3 authors, Sandra B Horowitz.
Pharmacotherapy, 2017 Jan 13; 37(3). PMID: 28079265
Review.
Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity.
A Diefenbach, E R Jensen, A M Jamieson, D H Raulet.
Nature, 2001 Sep 15; 413(6852). PMID: 11557981    Free PMC article.
Highly Cited.
Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.
Erica L Bradshaw, Mary E Spilker, +11 authors, Jason R Chan.
CPT Pharmacometrics Syst Pharmacol, 2019 Sep 20; 8(11). PMID: 31535440    Free PMC article.
The potential of tumour microenvironment markers to stratify the risk of recurrence in prostate cancer patients.
Thomas Gevaert, Yves-Rémi Van Eycke, +8 authors, Christine Decaestecker.
PLoS One, 2020 Dec 29; 15(12). PMID: 33370412    Free PMC article.
QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.
Richard J Sové, Mohammad Jafarnejad, +3 authors, Aleksander S Popel.
CPT Pharmacometrics Syst Pharmacol, 2020 Jul 04; 9(9). PMID: 32618119    Free PMC article.
Immune Evasion in Pancreatic Cancer: From Mechanisms to Therapy.
Neus Martinez-Bosch, Judith Vinaixa, Pilar Navarro.
Cancers (Basel), 2018 Jan 06; 10(1). PMID: 29301364    Free PMC article.
Highly Cited. Review.
Role of LAG-3 in regulatory T cells.
Ching-Tai Huang, Creg J Workman, +11 authors, Dario A A Vignali.
Immunity, 2004 Oct 16; 21(4). PMID: 15485628
Highly Cited.
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition.
Elizabeth I Buchbinder, Anupam Desai.
Am J Clin Oncol, 2015 Nov 13; 39(1). PMID: 26558876    Free PMC article.
Highly Cited. Review.
Population Pharmacokinetic/Pharmacodynamic Modeling of Tumor Size Dynamics in Pembrolizumab-Treated Advanced Melanoma.
M S Chatterjee, J Elassaiss-Schaap, +9 authors, D P de Alwis.
CPT Pharmacometrics Syst Pharmacol, 2016 Nov 30; 6(1). PMID: 27896938    Free PMC article.
Nonlinear dynamics of immunogenic tumors: parameter estimation and global bifurcation analysis.
V A Kuznetsov, I A Makalkin, M A Taylor, A S Perelson.
Bull Math Biol, 1994 Mar 01; 56(2). PMID: 8186756
Mode-of-action, efficacy, and safety of a homologous multi-epitope vaccine in a murine model for adjuvant treatment of renal cell carcinoma.
Christian Doehn, Norbert Esser, +5 authors, Joachim Drevs.
Eur Urol, 2008 Jun 14; 56(1). PMID: 18550267
A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.
Xuefang Li, Jian-Xin Xu.
J Theor Biol, 2016 Jun 25; 406. PMID: 27338302
Mathematical model of tumor-immune surveillance.
Khaphetsi Joseph Mahasa, Rachid Ouifki, Amina Eladdadi, Lisette de Pillis.
J Theor Biol, 2016 Jun 19; 404. PMID: 27317864
Immune Cell Population in Ovarian Tumor Microenvironment.
Dong Li Cai, Li-Ping Jin.
J Cancer, 2017 Sep 21; 8(15). PMID: 28928882    Free PMC article.
Review.
Conducting a Virtual Clinical Trial in HER2-Negative Breast Cancer Using a Quantitative Systems Pharmacology Model With an Epigenetic Modulator and Immune Checkpoint Inhibitors.
Hanwen Wang, Richard J Sové, +6 authors, Aleksander S Popel.
Front Bioeng Biotechnol, 2020 Mar 12; 8. PMID: 32158754    Free PMC article.
Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2.
Richard A Morgan, James C Yang, +3 authors, Steven A Rosenberg.
Mol Ther, 2010 Feb 25; 18(4). PMID: 20179677    Free PMC article.
Highly Cited.
Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells.
Claudia Wrzesinski, Chrystal M Paulos, +6 authors, Nicholas P Restifo.
J Immunother, 2009 Dec 03; 33(1). PMID: 19952961    Free PMC article.
Highly Cited.
Costimulatory molecule requirement for bovine WC1+gammadelta T cells' proliferative response to bacterial superantigens.
Y Fikri, P-P Pastoret, J Nyabenda.
Scand J Immunol, 2002 Apr 23; 55(4). PMID: 11967119
Lymphocyte-activation gene-3, an important immune checkpoint in cancer.
Yayi He, Christopher J Rivard, +5 authors, Fred R Hirsch.
Cancer Sci, 2016 Jun 15; 107(9). PMID: 27297395    Free PMC article.
Highly Cited. Review.
Use of translational modeling and simulation for quantitative comparison of PF-06804103, a new generation HER2 ADC, with Trastuzumab-DM1.
Alison Betts, Tracey Clark, +7 authors, Frank Barletta.
J Pharmacokinet Pharmacodyn, 2020 Jul 28; 47(5). PMID: 32710210    Free PMC article.
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
Li Wang, Rotem Rubinstein, +10 authors, Randolph J Noelle.
J Exp Med, 2011 Mar 09; 208(3). PMID: 21383057    Free PMC article.
Highly Cited.
Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.
E J Small, P Fratesi, +4 authors, F H Valone.
J Clin Oncol, 2000 Dec 01; 18(23). PMID: 11099318
Highly Cited.
A validated mathematical model of cell-mediated immune response to tumor growth.
Lisette G de Pillis, Ami E Radunskaya, Charles L Wiseman.
Cancer Res, 2005 Sep 06; 65(17). PMID: 16140967
Pembrolizumab: Role of Modeling and Simulation in Bringing a Novel Immunotherapy to Patients With Melanoma.
R de Greef, J Elassaiss-Schaap, +7 authors, J Stone.
CPT Pharmacometrics Syst Pharmacol, 2016 Sep 23; 6(1). PMID: 27653180    Free PMC article.
Review.
Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option.
Maartje W Rohaan, Joost H van den Berg, Pia Kvistborg, John B A G Haanen.
J Immunother Cancer, 2018 Oct 05; 6(1). PMID: 30285902    Free PMC article.
Review.
In silico simulation of a clinical trial with anti-CTLA-4 and anti-PD-L1 immunotherapies in metastatic breast cancer using a systems pharmacology model.
Hanwen Wang, Oleg Milberg, +6 authors, Aleksander S Popel.
R Soc Open Sci, 2019 Jun 21; 6(5). PMID: 31218069    Free PMC article.
Modeling tumor response after combined administration of different immune-stimulatory agents.
Zinnia P Parra-Guillen, Pedro Berraondo, Benjamin Ribba, Iñaki F Trocóniz.
J Pharmacol Exp Ther, 2013 Jul 13; 346(3). PMID: 23845890
Immuno-Oncology: Emerging Targets and Combination Therapies.
Henry T Marshall, Mustafa B A Djamgoz.
Front Oncol, 2018 Sep 08; 8. PMID: 30191140    Free PMC article.
Highly Cited. Review.
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer.
Jianjun Gao, John F Ward, +16 authors, Padmanee Sharma.
Nat Med, 2017 Mar 28; 23(5). PMID: 28346412    Free PMC article.
Highly Cited.
First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity.
Chrystelle Brignone, Maya Gutierrez, +9 authors, Frédéric Triebel.
J Transl Med, 2010 Jul 27; 8. PMID: 20653948    Free PMC article.
VISTA expressed in tumour cells regulates T cell function.
Kumuluzi Mulati, Junzo Hamanishi, +14 authors, Masaki Mandai.
Br J Cancer, 2018 Nov 02; 120(1). PMID: 30382166    Free PMC article.
Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients.
Julien Fourcade, Zhaojun Sun, +6 authors, Hassane M Zarour.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819923    Free PMC article.
Highly Cited.
Modeling immunotherapy of the tumor-immune interaction.
D Kirschner, J C Panetta.
J Math Biol, 1998 Oct 24; 37(3). PMID: 9785481
An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection.
Peggy Han, Olivia D Goularte, +2 authors, Jonathan Kaye.
J Immunol, 2004 May 07; 172(10). PMID: 15128774
Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients--Report of a Phase I/IIa Clinical Trial.
Amandine Legat, Hélène Maby-El Hajjami, +15 authors, Daniel E Speiser.
Clin Cancer Res, 2015 Oct 27; 22(6). PMID: 26500235
Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma.
Peng Gao, Qiang Ding, +2 authors, Zujun Fang.
Cancer Lett, 2009 Sep 30; 290(2). PMID: 19786319
Population pharmacokinetic-pharmacodynamic modelling in oncology: a tool for predicting clinical response.
Brendan C Bender, Emilie Schindler, Lena E Friberg.
Br J Clin Pharmacol, 2013 Oct 19; 79(1). PMID: 24134068    Free PMC article.
Review.
Mathematical model of BCG immunotherapy in superficial bladder cancer.
Svetlana Bunimovich-Mendrazitsky, Eliezer Shochat, Lewi Stone.
Bull Math Biol, 2007 Apr 26; 69(6). PMID: 17457655
BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.
Laurent Derré, Jean-Paul Rivals, +6 authors, Daniel E Speiser.
J Clin Invest, 2009 Dec 30; 120(1). PMID: 20038811    Free PMC article.
Highly Cited.
Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2.
S A Rosenberg, J R Yannelli, +7 authors, D E White.
J Natl Cancer Inst, 1994 Aug 03; 86(15). PMID: 8028037
Highly Cited.
Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.
Anna H-X P Chan Kwong, Elisa A M Calvier, +2 authors, Sonia Khier.
J Pharmacokinet Pharmacodyn, 2020 Jun 15; 47(5). PMID: 32535847    Free PMC article.
Review.
Prediction of the Optimal Dosing Regimen Using a Mathematical Model of Tumor Uptake for Immunocytokine-Based Cancer Immunotherapy.
Benjamin Ribba, Christophe Boetsch, +9 authors, Volker Teichgräber.
Clin Cancer Res, 2018 Feb 22; 24(14). PMID: 29463551
Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) can play a direct role in the inhibitory function of killer cell Ig-like receptors in human NK cells.
Sei-Ichi Yusa, Kerry S Campbell.
J Immunol, 2003 Apr 23; 170(9). PMID: 12707331
Immune Infiltration and Prostate Cancer.
Amy Strasner, Michael Karin.
Front Oncol, 2015 Jul 29; 5. PMID: 26217583    Free PMC article.
Highly Cited. Review.
Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma.
Lei Wu, Wei-Wei Deng, +6 authors, Zhi-Jun Sun.
Cancer Immunol Immunother, 2017 Feb 27; 66(5). PMID: 28236118
Quantitative Systems Pharmacology Model of Chimeric Antigen Receptor T-Cell Therapy.
Deni Hardiansyah, Chee Meng Ng.
Clin Transl Sci, 2019 Apr 17; 12(4). PMID: 30990958    Free PMC article.
Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies.
Roberta Zappasodi, Taha Merghoub, Jedd D Wolchok.
Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634946    Free PMC article.
Highly Cited. Review.
Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.
Steven A Rosenberg, James C Yang, +12 authors, Mark E Dudley.
Clin Cancer Res, 2011 Apr 19; 17(13). PMID: 21498393    Free PMC article.
Highly Cited.
A PK/PD Analysis of Circulating Biomarkers and Their Relationship to Tumor Response in Atezolizumab-Treated non-small Cell Lung Cancer Patients.
Ida Netterberg, Chi-Chung Li, +5 authors, Lena E Friberg.
Clin Pharmacol Ther, 2018 Jul 31; 105(2). PMID: 30058723    Free PMC article.
A guide to cancer immunotherapy: from T cell basic science to clinical practice.
Alex D Waldman, Jill M Fritz, Michael J Lenardo.
Nat Rev Immunol, 2020 May 21; 20(11). PMID: 32433532    Free PMC article.
Review.
Immune checkpoint inhibitor combinations: Current efforts and important aspects for success.
Edo Kon, Itai Benhar.
Drug Resist Updat, 2019 Aug 06; 45. PMID: 31382144
Review.
Quantitative Systems Pharmacology Approaches for Immuno-Oncology: Adding Virtual Patients to the Development Paradigm.
Vijayalakshmi Chelliah, Georgia Lazarou, +36 authors, Andrzej M Kierzek.
Clin Pharmacol Ther, 2020 Jul 21; 109(3). PMID: 32686076    Free PMC article.
Review.
Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy.
Pierre G Coulie, Benoît J Van den Eynde, Pierre van der Bruggen, Thierry Boon.
Nat Rev Cancer, 2014 Jan 25; 14(2). PMID: 24457417
Highly Cited. Review.
Translational Pharmacokinetic/Pharmacodynamic Modeling of Tumor Growth Inhibition Supports Dose-Range Selection of the Anti-PD-1 Antibody Pembrolizumab.
A Lindauer, C R Valiathan, +4 authors, D P de Alwis.
CPT Pharmacometrics Syst Pharmacol, 2016 Nov 20; 6(1). PMID: 27863176    Free PMC article.
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.
Highly Cited.
Oncology meets immunology: the cancer-immunity cycle.
Daniel S Chen, Ira Mellman.
Immunity, 2013 Jul 31; 39(1). PMID: 23890059
Highly Cited. Review.
Chemotherapy and/or immune checkpoint inhibitors in NSCLC first-line setting: what is the best approach?
Luigi Della Gravara, Ciro Battiloro, +4 authors, Danilo Rocco.
Lung Cancer Manag, 2020 Apr 08; 9(1). PMID: 32256708    Free PMC article.
Mixed immunotherapy and chemotherapy of tumors: modeling, applications and biological interpretations.
L G de Pillis, W Gu, A E Radunskaya.
J Theor Biol, 2005 Sep 13; 238(4). PMID: 16153659
A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma.
Mark E Dudley, John R Wunderlich, +13 authors, Steven A Rosenberg.
J Immunother, 2002 May 10; 25(3). PMID: 12000866    Free PMC article.
Signatures of mutational processes in human cancer.
Ludmil B Alexandrov, Serena Nik-Zainal, +72 authors, Michael R Stratton.
Nature, 2013 Aug 16; 500(7463). PMID: 23945592    Free PMC article.
Highly Cited.
Quantitative Mechanistic Modeling in Support of Pharmacological Therapeutics Development in Immuno-Oncology.
Kirill Peskov, Ivan Azarov, +3 authors, Gabriel Helmlinger.
Front Immunol, 2019 May 28; 10. PMID: 31134058    Free PMC article.
Review.
Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience.
Cor H J Lamers, Stefan Sleijfer, +6 authors, Egbert Oosterwijk.
J Clin Oncol, 2006 May 02; 24(13). PMID: 16648493
Highly Cited.
Personal response to immune checkpoint inhibitors of patients with advanced melanoma explained by a computational model of cellular immunity, tumor growth, and drug.
D Perlstein, O Shlagman, +4 authors, Z Agur.
PLoS One, 2019 Dec 27; 14(12). PMID: 31877168    Free PMC article.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
Kaori Sakuishi, Lionel Apetoh, +3 authors, Ana C Anderson.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819927    Free PMC article.
Highly Cited.
TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action.
Wenwen Du, Min Yang, +5 authors, Binfeng Lu.
Int J Mol Sci, 2017 Mar 17; 18(3). PMID: 28300768    Free PMC article.
Review.
Differential effect of CD8(+) and CD8(-) dendritic cells in the stimulation of secondary CD4(+) T cells.
V Kronin, C J Fitzmaurice, +3 authors, L E Brown.
Int Immunol, 2001 Apr 03; 13(4). PMID: 11282986
Update on immune checkpoint inhibitors in gynecological cancers.
Valerie Heong, Natalie Ngoi, David Shao Peng Tan.
J Gynecol Oncol, 2016 Dec 29; 28(2). PMID: 28028993    Free PMC article.
Review.
Adoptive cell transfer as personalized immunotherapy for human cancer.
Steven A Rosenberg, Nicholas P Restifo.
Science, 2015 Apr 04; 348(6230). PMID: 25838374    Free PMC article.
Highly Cited. Review.
A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
P G Coulie, V Brichard, +9 authors, T Boon.
J Exp Med, 1994 Jul 01; 180(1). PMID: 8006593    Free PMC article.
Highly Cited.
Chimeric antigen receptor engineering: a right step in the evolution of adoptive cellular immunotherapy.
Jose A Figueroa, Adair Reidy, +16 authors, Maurizio Chiriva-Internati.
Int Rev Immunol, 2015 Apr 23; 34(2). PMID: 25901860
Review.
TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients.
Pia Kvistborg, Chengyi Jenny Shu, +19 authors, Ton N M Schumacher.
Oncoimmunology, 2012 Jul 04; 1(4). PMID: 22754759    Free PMC article.
TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy.
William C Dougall, Sema Kurtulus, Mark J Smyth, Ana C Anderson.
Immunol Rev, 2017 Mar 05; 276(1). PMID: 28258695
Highly Cited. Review.
VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML.
Liru Wang, Bei Jia, +9 authors, Hong Zheng.
Oncoimmunology, 2018 Sep 20; 7(9). PMID: 30228937    Free PMC article.
Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model.
Svetlana Bunimovich-Mendrazitsky, Sarel Halachmi, Natalie Kronik.
Math Med Biol, 2015 Apr 19; 33(2). PMID: 25888550
Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.
Xianjie Jiang, Jie Wang, +12 authors, Zhaoyang Zeng.
Mol Cancer, 2019 Jan 17; 18(1). PMID: 30646912    Free PMC article.
Highly Cited. Review.
Using Model-Based "Learn and Confirm" to Reveal the Pharmacokinetics-Pharmacodynamics Relationship of Pembrolizumab in the KEYNOTE-001 Trial.
J Elassaiss-Schaap, S Rossenu, +4 authors, D P de Alwis.
CPT Pharmacometrics Syst Pharmacol, 2016 Nov 20; 6(1). PMID: 27863143    Free PMC article.