Opportunities for Small Molecules in Cancer Immunotherapy

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157

Cancer immunotherapy using checkpoint blockade

Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791

Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212

The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells

Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145

The future of immune checkpoint therapy

Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849

Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer

Paz-Ares, L., Luft, A., Vicente, D., Tafreshi, A., Gümüş, M., Mazières, J., Hermes, B., Çay Şenler, F., Csőszi, T., Fülöp, A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1810865 · Cited by 3,617

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

McGranahan, N., Furness, A. J. S., Rosenthal, R., Ramskov, S., Lyngaa, R., Saini, S. K., Jamal-Hanjani, M., Wilson, G. A., Birkbak, N. J., Hiley, C. T., et al. (2016) · Science · doi:10.1126/science.aaf1490 · Cited by 3,065

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

Sahin, U., Derhovanessian, E., Miller, M., Kloke, B.-P., Simon, P., Löwer, M., Bukur, V., Tadmor, A. D., Luxemburger, U., Schrörs, B., et al. (2017) · Nature · doi:10.1038/nature23003 · Cited by 2,488

Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase

Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305

Durable Clinical Benefit with Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer

Overman, M. J., Lonardi, S., Wong, K. Y. M., Lenz, H.-J., Gelsomino, F., Aglietta, M., Morse, M. A., Van Cutsem, E., McDermott, R., Hill, A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.9901 · Cited by 2,079

STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors

Woo, S.-R., Fuertes, M. B., Corrales, L., Spranger, S., Furdyna, M. J., Leung, M. Y. K., Duggan, R., Wang, Y., Barber, G. N., Fitzgerald, K. A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.017 · Cited by 1,917

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898

Phthalimide conjugation as a strategy for in vivo target protein degradation

Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760

T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689

CD4+ T cell help in cancer immunology and immunotherapy

Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585

Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

Corrales, L., Glickman, L. H., McWhirter, S. M., Kanne, D. B., Sivick, K. E., Katibah, G. E., Woo, S.-R., Lemmens, E., Banda, T., Leong, J. J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.031 · Cited by 1,560

Immunological effects of conventional chemotherapy and targeted anticancer agents

Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.012 · Cited by 1,530

Adaptive immunity maintains occult cancer in an equilibrium state

Koebel, C. M., Vermi, W., Swann, J. B., Zerafa, N., Rodig, S. J., Old, L. J., Smyth, M. J., & Schreiber, R. D. (2007) · Nature · doi:10.1038/nature06309 · Cited by 1,438

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

Keskin, D. B., Anandappa, A. J., Sun, J., Tirosh, I., Mathewson, N. D., Li, S., Oliveira, G., Giobbie-Hurder, A., Felt, K., Gjini, E., et al. (2019) · Nature · doi:10.1038/s41586-018-0792-9 · Cited by 1,432

Therapeutic cancer vaccines

Melief, C. J. M., van Hall, T., Arens, R., OSSENDORP, F. A., & van der Burg, S. H. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80009 · Cited by 1,192

A2A adenosine receptor protects tumors from antitumor T cells

Ohta, A., Gorelik, E., Prasad, S. J., Ronchese, F., Lukashev, D. E., Wong, M. K. K., Huang, X., Caldwell, S. A., Liu, K., Smith, P. T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605251103 · Cited by 1,095

Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

Sistigu, A., Yamazaki, T., Vacchelli, E., Chaba, K., Enot, D. P., Adam, J., Vitale, I., Goubar, A., Baracco, E. E., Remédios, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3708 · Cited by 1,042

PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression

Jiao, S., Xia, W., Yamaguchi, H., Wei, Y., Chen, M.-K., Hsu, J.-M., Hsu, J. L., Yu, W.-H., Du, Y., Lee, H.-H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3215 · Cited by 981

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study

Long, G. V., Dummer, R., Hamid, O., Gajewski, T. F., Caglevic, C., Dalle, S., Arance, A., Carlino, M. S., Grob, J.-J., Kim, T. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30274-8 · Cited by 960

Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial

Voorwerk, L., Slagter, M., Horlings, H. M., Sikorska, K., de Vijver, K. K. V., de Maaker, M., Nederlof, I., Kluin, R. J. C., Warren, S., Ong, S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0432-4 · Cited by 932

Cytokine patterns in patients with cancer: a systematic review

Lippitz, B. E. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70582-x · Cited by 922

Design of amidobenzimidazole STING receptor agonists with systemic activity

Ramanjulu, J. M., Pesiridis, G. S., Yang, J., Concha, N., Singhaus, R., Zhang, S.-Y., Tran, J.-L., Moore, P., Lehmann, S., Eberl, H. C., et al. (2018) · Nature · doi:10.1038/s41586-018-0705-y · Cited by 912

CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma

Steele, C. W., Karim, S. A., Leach, J. D. G., Bailey, P. J., Upstill‐Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.014 · Cited by 857

CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation

Deng, J., Wang, E. S., Jenkins, R. W., Li, S., Dries, R., Yates, K., Chhabra, S., Huang, W., Liu, H., Aref, A. R., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0915 · Cited by 770

Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX Inhibitors

Lou, Y., McDonald, P. C., Oloumi, A., Chia, S., Ostlund, C., Ahmadi, A., Kyle, A. H., Keller, U. A. D., Leung, S., Huntsman, D. D., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4261 · Cited by 761

The clinical role of the TME in solid cancer

Giraldo, N. A., Sánchez-Salas, R., Peske, J. D., Vano, Y. A., Becht, É., Petitprez, F., Validire, P., Ingels, A., Cathelineau, X., Fridman, W. H., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0327-z · Cited by 756

Hypoxia-Inducible Carbonic Anhydrase IX and XII Promote Tumor Cell Growth by Counteracting Acidosis through the Regulation of the Intracellular pH

Chiche, J., Ilc, K., Laferrière, J., Trottier, E., Dayan, F., Mazure, N. M., Brahimi-Horn, M. C., & Pouysségur, J. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2470 · Cited by 751

Immunogenicity of somatic mutations in human gastrointestinal cancers

Tran, E., Ahmadzadeh, M., Lu, Y.-C., Gros, A., Turcotte, S., Robbins, P. F., Gartner, J. J., Zheng, Z., Li, Y. F., Ray, S., et al. (2015) · Science · doi:10.1126/science.aad1253 · Cited by 729

Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Molon, B., Ugel, S., Pozzo, F. D., Soldani, C., Zilio, S., Avella, D., Palma, A. D., Mauri, P., Monegal, A., Rescigno, M., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101956 · Cited by 685

Small‐Molecule PROTACS: New Approaches to Protein Degradation

Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674

Nuclear cGAS suppresses DNA repair and promotes tumorigenesis

Liu, H., Zhang, H., Wu, X., Ma, D., Wu, J., Wang, L., Jiang, Y., Fei, Y., Zhu, C., Tan, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0629-6 · Cited by 672

Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909

Speiser, D. E., Líénard, D., Rufer, N., Rubio‐Godoy, V., Rimoldi, D., Lejeune, F. J., Krieg, A. Μ., Cerottini, J., & Romero, P. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23373 · Cited by 647

Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors

Heinhuis, K. M., Ros, W., Kok, M., Steeghs, N., Beijnen, J. H., & Schellens, J. H. M. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy551 · Cited by 563

Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs

Li, L., Yin, Q., Kuss, P., Maliga, Z., Millán, J. L., Wu, H., & Mitchison, T. J. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1661 · Cited by 545

Regulation of T Cell Receptor CD3ζ Chain Expression byl-Arginine

Rodrı́guez, P. C., Zea, A. H., Culotta, K. S., Zabaleta, J., Ochoa, J. B., & Ochoa, A. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110675200 · Cited by 537

Tumor-repopulating cells induce PD-1 expression in CD8(+) T cells by transferring kynurenine and AhR activation

Liu, Y., Liang, X., Dong, W., Fang, Y., Lv, J., Zhang, T., Fiskesund, R., Xie, J., Liu, J., Yin, X., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.005 · Cited by 535

Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway

Hogenesch, J. B., Chan, W. K., Jackiw, V., Brown, R. C., Gu, Y.-Z., Pray-Grant, M. G., Perdew, G. H., & Bradfield, C. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8581 · Cited by 514

Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment

Steggerda, S. M., Bennett, M. K., Chen, J., Emberley, E. D., Huang, T. C., Janes, J. R., Li, W., MacKinnon, A. L., Makkouk, A., Marguier, G. M., et al. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0308-4 · Cited by 503

Big opportunities for small molecules in immuno-oncology

Adams, J. L., Smothers, J. F., Srinivasan, R., & Hoos, A. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4596 · Cited by 492

Recent advances in arginine metabolism: roles and regulation of the arginases

Morris Jr, S. M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00278.x · Cited by 485

CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis

Katoh, H., Wang, D., Daikoku, T., Sun, H., Dey, S. K., & DuBois, R. N. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.10.009 · Cited by 477

Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

Żak, K. M., Grudnik, P., Guzik, K., Zieba, B. J., Musielak, B., Dömling, A. S. S., Dubin, G., & Holak, T. A. (2016) · Oncotarget · doi:10.18632/oncotarget.8730 · Cited by 453

CXCR4 inhibition in tumor microenvironment facilitates anti‐programmed death receptor‐1 immunotherapy in sorafenib‐treated hepatocellular carcinoma in mice

Chen, Y., Ramjiawan, R. R., Reiberger, T., Ng, M. R., Hato, T., Huang, Y., Ochiai, H., Kitahara, S., Unan, E. C., Reddy, T. P., et al. (2015) · Hepatology · doi:10.1002/hep.27665 · Cited by 451

Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma

Chiu, D. K.-C., Tse, A. P.-W., Xu, I. M.-J., Di Cui, J., Lai, R. K.-H., Li, L. L., Koh, H.-Y., Tsang, F. H.-C., Wei, L. L., Wong, C.-M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00530-7 · Cited by 448

IDO1 in cancer: a Gemini of immune checkpoints

Zhai, L., Ladomersky, E., Lenzen, A. C., Nguyen, B., Patel, R., Lauing, K. L., Wu, M., & Wainwright, D. A. (2018) · Cellular and Molecular Immunology · doi:10.1038/cmi.2017.143 · Cited by 448

Doxorubicin Eliminates Myeloid-Derived Suppressor Cells and Enhances the Efficacy of Adoptive T-Cell Transfer in Breast Cancer

Alizadeh, D., Trad, M., Hanke, N. T., Larmonier, C. B., Janikashvili, N., Bonnotte, B., Katsanis, E., & Larmonier, N. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1545 · Cited by 416

Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies

Liston, D. R., & Davis, M. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3083 · Cited by 402

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia

Uy, G. L., Rettig, M. P., Motabi, I., McFarland, K., Trinkaus, K. M., Hladnik, L. M., Kulkarni, S., Abboud, C. N., Cashen, A. F., Stockerl-Goldstein, K. E., et al. (2012) · Blood · doi:10.1182/blood-2011-10-383406 · Cited by 399

The development and immunosuppressive functions of CD4+ CD25+ FoxP3+ regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway

Ohta, A., Kini, R., Ohta, A., Subramanian, M., Madasu, M. M., & Sitkovsky, M. V. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00190 · Cited by 398

Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma

Courtney, K. D., Infante, J. R., Lam, E. T., Figlin, R. A., Rini, B. I., Brugarolas, J., Zojwalla, N. J., Lowe, A. M., Wang, K., Wallace, E. M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.2627 · Cited by 393

Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1

Guzik, K., Żak, K. M., Grudnik, P., Magiera‐Mularz, K., Musielak, B., Törner, R., Skalniak, Ł., Dömling, A. S. S., Dubin, G., & Holak, T. A. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00293 · Cited by 385

TLR agonists: our best frenemy in cancer immunotherapy

Kaczanowska, S., Joseph, A. M., & Dávila, E. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1012501 · Cited by 352

STING Promotes the Growth of Tumors Characterized by Low Antigenicity via IDO Activation

Lemos, H. D. P., Mohamed, E. T., Huang, L., Ou, R., Pacholczyk, G. A., Arbab, A. S., Munn, D. H., & Mellor, A. L. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1456 · Cited by 325

Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations

Karzai, F. H., VanderWeele, D. J., Madan, R. A., Owens, H., Cordes, L. M., Hankin, A., Couvillon, A., Nichols, E. H., Bilušić, M., Beshiri, M. L., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0463-2 · Cited by 311

Targeting CXCL12/CXCR4 Axis in Tumor Immunotherapy

Zhou, W., Guo, S., Liu, M., Burow, M. E., & Wang, G. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170830111531 · Cited by 286

Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination

Santo, C. D., Serafini, P., Marigo, I., Dolcetti, L., Bolla, M., Soldato, P. D., Melani, C. C., Guiducci, C., Colombo, M. P., Iezzi, M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409783102 · Cited by 284

Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer

Prendergast, G. C., Malachowski, W. P., Mondal, A., Scherle, P., & Muller, A. J. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.07.004 · Cited by 277

The paradox of Th17 cell functions in tumor immunity

Asadzadeh, Z., Mohammadi, H., Safarzadeh, E., Hemmatzadeh, M., Mahdian-shakib, A., Jadidi‐Niaragh, F., Azizi, G., & Baradaran, B. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.10.015 · Cited by 238

Trial Watch: Toll-like receptor agonists in cancer immunotherapy

Smith, M. M., García-Martínez, E., Pitter, M. R., Fucikova, J. P., Špíšek, R., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1526250 · Cited by 237

Cyclooxygenase‐2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

Pang, L. Y., Hurst, E. A., & Argyle, D. J. (2016) · Stem Cells International · doi:10.1155/2016/2048731 · Cited by 201

Immunomodulators targeting the PD‐1/PD‐L1 protein‐protein interaction: From antibodies to small molecules

Yang, J., & Hu, L. (2018) · Medicinal Research Reviews · doi:10.1002/med.21530 · Cited by 201

Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model

Dubois, L. J., Lieuwes, N. G., Maresca, A., Thiry, A., Supuran, C. T., Scozzafava, A., Wouters, B. G., & Lambin, P. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.06.019 · Cited by 195

STING agonist therapy in combination with PD-1 immune checkpoint blockade enhances response to carboplatin chemotherapy in high-grade serous ovarian cancer

Ghaffari, A., Peterson, N. T., Khalaj, K., Vitkin, N., Robinson, A. G., Francis, J., & Koti, M. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0188-5 · Cited by 188

PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma

Ruf, M., Moch, H., & Schraml, P. (2016) · International Journal of Cancer · doi:10.1002/ijc.30077 · Cited by 179

Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance

Hennequart, M., Pilotte, L., Canè, S., Hoffmann, D., Stroobant, V., Plaen, E. D., & den Eynde, B. J. V. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0400 · Cited by 176

A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors

Soliman, H. H., Jackson, E., Neuger, T., Dees, E. C., Harvey, R. D., Han, H., Ismail-Khan, R., Minton, S., Vahanian, N. N., Link, C., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2357 · Cited by 174

In vitroandin vivocharacterization of PF‐04418948, a novel, potent and selective prostaglandin EP2receptor antagonist

af Forselles, K., Root, J. A., Clarke, T. L., Davey, D. A., Aughton, K., Dack, K. N., & Pullen, N. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01495.x · Cited by 164

Small Molecules Drive Big Improvements in Immuno‐Oncology Therapies

Huck, B. R., Kötzner, L., & Urbahns, K. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201707816 · Cited by 154

Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells

Krombach, J., Hennel, R., Brix, N., Orth, M., Schötz, U., Ernst, A., Schuster, J., Zuchtriegel, G., Reichel, C. A., Bierschenk, S., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1523097 · Cited by 138

Tumor Eradication by Cisplatin Is Sustained by CD80/86-Mediated Costimulation of CD8+ T Cells

Nejad, E. B., van der Sluis, T. C., van Duikeren, S., Yagita∥, H., Janssen, G. M. C., van Veelen, P. A., Melief, C. J. M., van der Burg, S. H., & Arens, R. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0881 · Cited by 137

Comprehensive in vitro characterization of PD-L1 small molecule inhibitors

Ganesan, A., Ahmed, M., Okoye, I., Arutyunova, E. I., Babu, D., Turnbull, W. L., Kundu, J. K., Shields, J. A., Agopsowicz, K. C., Xu, L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-48826-6 · Cited by 136

Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells

Onoue, T., Uchida, D., Begum, N., Tomizuka, Y., Yoshida, H., & Sato, M. (2006) · International Journal of Oncology · doi:10.3892/ijo.29.5.1133 · Cited by 134

The Next Generation of Immunotherapy for Cancer: Small Molecules Could Make Big Waves

Kerr, W. G., & Chisholm, J. D. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1800991 · Cited by 131

Clinical pharmacology considerations for the development of immune checkpoint inhibitors

Sheng, J., Srivastava, S., Sanghavi, K., Lu, Z., Schmidt, B. J., Bello, A., & Gupta, M. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.990 · Cited by 124

A chemical approach for global protein knockdown from mice to non-human primates

Sun, X., Wang, J., Yao, X., Zheng, W., Mao, Y., Lan, T., Wang, L., Sun, Y., Zhang, X., Zhao, Q., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0079-1 · Cited by 118

Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck

Ferris, R. L., Saba, N. F., Gitlitz, B. J., Haddad, R. I., Sukari, A. W., Neupane, P. C., Morris, J. C., Misiukiewicz, K. J., Bauman, J. E., Fenton, M. J., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.1888 · Cited by 113

Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity

Hu, X., Liu, X., Moisan, J., Wang, Y., Lesch, C. A., Spooner, C. J., Morgan, R. W., Zawidzka, E. M., Mertz, D. R., Bousley, D., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1254854 · Cited by 107

Antagonists of the Human A2A Adenosine Receptor. 4. Design, Synthesis, and Preclinical Evaluation of 7-Aryltriazolo[4,5-d]pyrimidines

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CXCR2+ MDSCs promote breast cancer progression by inducing EMT and activated T cell exhaustion

Zhu, H., Gu, Y., Xue, Y., Yuan, M., Cao, X., & Liu, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.23020 · Cited by 102

Efficient Induction of Antitumor Immunity by Synthetic Toll-like Receptor Ligand–Peptide Conjugates

Zom, G. G., Khan, S., Britten, C. M., Sommandas, V., Camps, M. G. M., Loof, N. M., Budden, C. F., Meeuwenoord, N. J., Filippov, D. V., van der Marel, G. A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0223 · Cited by 101

Vinorelbine, cyclophosphamide and 5-FU effects on the circulating and intratumoural landscape of immune cells improve anti-PD-L1 efficacy in preclinical models of breast cancer and lymphoma

Orecchioni, S., Talarico, G., Labanca, V., Calleri, A., Mancuso, P., & Bertolini, F. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0076-z · Cited by 101

A prostaglandin E (PGE) receptor EP4 antagonist protects natural killer cells from PGE2-mediated immunosuppression and inhibits breast cancer metastasis

Ma, X., Holt, D. M., Kundu, N., Reader, J. C., Goloubeva, O. G., Take, Y., & Fulton, A. M. (2013) · OncoImmunology · doi:10.4161/onci.22647 · Cited by 99

Dynamic Structural Differences between Human and Mouse STING Lead to Differing Sensitivity to DMXAA

Shih, A. Y., Damm‐Ganamet, K. L., & Mirzadegan, T. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2017.10.027 · Cited by 93

Pembrolizumab plus Chemotherapy in Lung Cancer

Gil-Sierra, M. D., Fenix-Caballero, S., & Rey, E. J. A. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmc1808567 · Cited by 89

Imidazopyridine- and Purine-Thioacetamide Derivatives: Potent Inhibitors of Nucleotide Pyrophosphatase/Phosphodiesterase 1 (NPP1)

Chang, L., Lee, S.-Y., Leonczak, P., Rozenski, J., Jonghe, S. D., Hanck, T., Müller, C. E., & Herdewijn, P. A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501434y · Cited by 86

Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8 Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals

Shayan, G., Kansy, B., Gibson, S. P., Srivastava, R. M., Bryan, J. K., Bauman, J. E., Ohr, J. P., Kim, S., Duvvuri, U., Clump, D. A., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0357 · Cited by 84

Rapid Onset of Inflammatory Bowel Disease after Receiving Secukinumab Infusion

Wang, J., Bhatia, A., Cleveland, N. K., Gupta, N., Dalal, S. R., Rubin, D. T., & Sakuraba, A. (2018) · ACG Case Reports Journal · doi:10.14309/crj.2018.56 · Cited by 75

Discovery of [cis-3-({(5R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor γt Inverse Agonist

Kono, M., Ochida, A., Oda, T., Imada, T., Banno, Y., Taya, N., Masada, S., Kawamoto, T., Yonemori, K., Nara, Y., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00061 · Cited by 72

Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: Current status and future considerations

Watt, G. F., Scott‐Stevens, P., & Gaohua, L. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.02.005 · Cited by 72

Ah Receptor Antagonism Represses Head and Neck Tumor Cell Aggressive Phenotype

DiNatale, B. C., Smith, K. M., John, K., Gowda, K., Amin, S., & Perdew, G. H. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0216 · Cited by 71

Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity

Dietsch, G. N., Lu, H., Yang, Y., Morishima, C., Chow, L. Q. M., Disis, M. L., & Hershberg, R. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148764 · Cited by 71

Targeting pattern-recognition receptors to discover new small molecule immune modulators

Zhu, G., Xu, Y., Cen, X., Nandakumar, K. S., Liu, S., & Cheng, K. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.12.026 · Cited by 68

Specific MHC-I Peptides Are Induced Using PROTACs

Jensen, S. M., Potts, G. K., Ready, D. B., & Patterson, M. J. S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02697 · Cited by 67

Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment

Miao, J., Xu, L., Hu, Y., Piao, C., Wu, X., Liu, X., Huang, C., Wang, Y., Li, D., & Liu, J. (2017) · Oncotarget · doi:10.18632/oncotarget.21155 · Cited by 66

CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2

Ghosh, M. C., Makena, P. S., Gorantla, V. K., Sinclair, S. E., & Waters, C. M. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00321.2011 · Cited by 65

New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors

Ciccarese, C., Alfieri, S., Santoni, M., Santini, D., Brunelli, M., Bergamini, C., Licitra, L. F., Montironi, R., Tortora, G., & Massari, F. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2016.1120287 · Cited by 62

CXCR4 antagonists suppress small cell lung cancer progression

Taromi, S., Kayser, G., Catusse, J., von Elverfeldt, D., Reichardt, W., Braun, F., Weber, W., Zeiser, R., & Burger, M. (2016) · Oncotarget · doi:10.18632/oncotarget.13238 · Cited by 62

Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities

Zhang, L. J., Dewan, V., & Yin, H. H. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00419 · Cited by 61

Synthetic RORγt Agonists Enhance Protective Immunity

Chang, M. R., Dharmarajan, V., Doebelin, C., Garcia-Ordoñez, R. D., Novick, S. J., Kuruvilla, D. S., Kamenecka, T. M., & Griffin, P. R. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.5b00899 · Cited by 59

Directing the Immune System with Chemical Compounds

Mancini, R. J., Stutts, L., Ryu, K. A., Tom, J. K., & Esser-Kahn, A. P. (2014) · ACS Chemical Biology · doi:10.1021/cb500079s · Cited by 57

Interleukin 17 and peripheral IL-17-expressing T cells are negatively correlated with the overall survival of head and neck cancer patients

Lee, M.-H., Chang, J. T., Liao, C., Chen, Y.-S., Kuo, M., & Shen, C. (2018) · Oncotarget · doi:10.18632/oncotarget.23934 · Cited by 53

Suppression of carbonic anhydrase IX leads to aberrant focal adhesion and decreased invasion of tumor cells

Radvák, P., Repic, M., Švastová, E., Takáčová, M., Csáderová, L., Strnad, H., Pastorek, J., Pastoreková, S., & Kopáček, J. (2013) · Oncology Reports · doi:10.3892/or.2013.2226 · Cited by 52

Prostaglandin EP2 receptor: Novel therapeutic target for human cancers (Review)

Sun, X., & Li, Q. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3744 · Cited by 50

Adoptive T Cell Therapy: New Avenues Leading to Safe Targets and Powerful Allies

Hammerl, D., Rieder, D., Martens, J. W. M., Trajanoski, Z., & Debets, R. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.09.004 · Cited by 46

Identification of Novel, Potent, and Orally Available GCN2 Inhibitors with Type I Half Binding Mode

Fujimoto, J., Kurasawa, O., Takagi, T., Liu, X., Banno, H., Kojima, T., Asano, Y., Nakamura, A., Nambu, T., Hata, A., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00400 · Cited by 44

Identification of Hepatic Niche Harboring Human Acute Lymphoblastic Leukemic Cells via the SDF-1/CXCR4 Axis

Kato, I., Niwa, A., Heike, T., Fujino, H., Saito, M. K., Umeda, K., Hiramatsu, H., Ito, M., Morita, M., Nishinaka, Y., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027042 · Cited by 42

Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer

Wang, R., Yang, L., Zhang, C., Wang, R., Zhang, Z., He, Q., Chen, X., Zhang, B., Qin, Z., Wang, L., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1461303 · Cited by 42

Inhibition of COX-2 and EGFR by Melafolone Improves Anti-PD-1 Therapy through Vascular Normalization and PD-L1 Downregulation in Lung Cancer

Tang, H., Liu, Y., Wang, C., Zheng, H., Chen, Y., Liu, W., Chen, X., Zhang, J., Chen, H., Yang, Y., et al. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.254359 · Cited by 41

Design, synthesis, and biological evaluation of C7-functionalized DMXAA derivatives as potential human-STING agonists

Hwang, J., Kang, T., Lee, J. H., Choi, B., & Han, S. (2018) · Organic & Biomolecular Chemistry · doi:10.1039/c8ob01798k · Cited by 39

Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells

Zom, G. G., Willems, M. M. J. H. P., Meeuwenoord, N. J., Reintjens, N. R. M., Tondini, E., Khan, S., Overkleeft, H. S., van der Marel, G. A., Codée, J. D. C., OSSENDORP, F. A., et al. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00087 · Cited by 34

Carboranyl Analogues of Celecoxib with Potent Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

Buzharevski, A., Paskaš, S., Sárosi, M. B., Laube, M., Lönnecke, P., Neumann, W., Mijatović, S., Maksimović‐Ivanić, D., Pietzsch, J., & Hey‐Hawkins, E. (2019) · ChemMedChem · doi:10.1002/cmdc.201800685 · Cited by 33

Therapeutic Potential of Small Molecule Inhibitors

Khera, N., & Rajput, S. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25782 · Cited by 32

Highly Selective and Potent Ectonucleotide Pyrophosphatase-1 (NPP1) Inhibitors Based on Uridine 5′-P α,α -Dithiophosphate Analogues

Zelikman, V., Pelletier, J., Simhaev, L., Sela, A., Gendron, F., Arguin, G., Senderowitz, H., Sévigny, J., & Fischer, B. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01906 · Cited by 32

Abstract CT177: Epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study

Naing, A., Powderly, J. D., Falchook, G. S., Creelan, B., Nemunaitis, J. J., Lutzky, J., Diab, A. K., Wang, J. S.-Z., Laing, N. M., Niewood, M., et al. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-ct177 · Cited by 26

Chemotherapy oxaliplatin sensitizes prostate cancer to immune checkpoint blockade therapies via stimulating tumor immunogenicity

Zhou, J., Yang, T., Liu, L., & Lu, B. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6908 · Cited by 23

Companies Scaling Back IDO1 Inhibitor Trials

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IDO-GCN2 and autophagy in inflammation

McGaha, T. L. (2015) · Oncotarget · doi:10.18632/oncotarget.4846 · Cited by 20

Relationship between epidermal growth factor receptor (EGFR) mutation and serum cyclooxygenase-2 Level, and the synergistic effect of celecoxib and gefitinib on EGFR expression in non-small cell lung cancer cells.

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PROTAC targeted protein degraders: the past is prologue

Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395

Successes and challenges in clinical gene therapy

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Drug combination therapy for emerging viral diseases

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Liposomal Delivery of Mitoxantrone and a Cholesteryl Indoximod Prodrug Provides Effective Chemo-immunotherapy in Multiple Solid Tumors

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Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations

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Role of small molecule-based drugs in cancer immunotherapy

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Cancer Immunotherapy: Selected Targets and Small‐Molecule Modulators

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Small-molecule agents for cancer immunotherapy

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Small-molecule in cancer immunotherapy: Revolutionizing cancer treatment with transformative, game-changing breakthroughs

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Research Advances on Small Molecule Targets for Tumor Immunotherapy

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