Targeting the Interplay between Epithelial-to-Mesenchymal-Transition and the Immune System for Effective Immunotherapy
Open accessAbstract
Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo- and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We discuss why, despite breakthrough progress in immunotherapy, attaining predictable outcomes in the clinic is mostly an unsolved problem for these tumors. Although these two cancer types appear different based upon their tissues of origin and molecular classification, gene expression indicate that they possess many similarities. Patient tumors exhibit activation of EMT, and resulting stem cell properties in both these cancer types associate with metastasis and resistance to existing cancer therapies. In addition, the EMT transition in both these cancers plays a crucial role in immunosuppression, which exacerbates treatment resistance. To improve cancer-related survival we need to understand and circumvent, the mechanisms through which these tumors become therapy resistant. In this review, we discuss new information and complementary perspectives to inform combination treatment strategies to expand and improve the anti-tumor responses of currently available clinical immune checkpoint inhibitors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
EMT enables carcinoma cells to exert local immunosuppression by repressing MHCI antigen presentation and antigen processing/presentation machinery, thereby suppressing CD8+ T cell and NK cytotoxic activities.
“Of further therapeutic relevance, EMT enables carcinoma cells to exert local immunosuppression143,144. EMT confers repression of major histocompatibility complex class I (MHCI) antigen presentation by tumor cells, which is required for recognition by CD8+ T cells, and thus indirectly suppresses cytotoxic activities of CD8+ T cells and cytolytic activities of NK cells141,143–145.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [143]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2017) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21387 · Cited by 14,712 · see citing works
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Robust enumeration of cell subsets from tissue expression profiles
Newman, A. M., Liu, C. L., Green, M. R., Gentles, A. J., Feng, W., Xu, Y., Hoang, C. D., Diehn, M., & Alizadeh, A. A. (2015) · Nature Methods · doi:10.1038/nmeth.3337 · Cited by 12,116 · see citing works
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089 · see citing works
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945 · cited 1× · see citing works
“There are data suggesting that PD-L1 expression on the tumor may be a biomarker predicting response to this class of therapy [19,20].”
BackgroundMutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802 · see citing works
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474 · see citing works
TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells
Li, T., Fan, J., Wang, B., Traugh, N. C., Chen, Q., Liu, J. S., Li, B., & Liu, X. S. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0307 · Cited by 5,914 · see citing works
Rittmeyer, A., Barlési, F., Waterkamp, D., Park, K., Ciardiello, F., von Pawel, J., Gadgeel, S. M., Hida, T., Kowalski, D. M., Cobo, M., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32517-x · Cited by 4,684 · see citing works
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652 · see citing works
Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer
Schmid, P., Adams, S., Rugo, H. S., Schneeweiss, A., Barrios, C. H., Iwata, H., Diéras, V., Hegg, R., Im, S.-A., Shaw Wright, G., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1809615 · Cited by 4,350 · see citing works
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229 · see citing works
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089 · see citing works
Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Yang, J., Mani, S. A., Donaher, J. L., Ramaswamy, S., Itzykson, R., Côme, C., Savagner, P., Gitelman, I., Richardson, A. L., & Weinberg, R. A. (2004) · Cell · doi:10.1016/j.cell.2004.06.006 · Cited by 3,856 · see citing works
Self-citationGregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., Vadas, M. A., Khew‐Goodall, Y., & Goodall, G. J. (2008) · Nature Cell Biology · doi:10.1038/ncb1722 · Cited by 3,852 · see citing works
Approaches to treat immune hot, altered and cold tumours with combination immunotherapies
Galon, J., & Bruni, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0007-y · Cited by 3,414 · see citing works
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121 · see citing works
The prognostic landscape of genes and infiltrating immune cells across human cancers
Gentles, A. J., Newman, A. M., Liu, C. L., Bratman, S. V., Feng, W., Kim, D., Nair, V. S., Xu, Y., Khuong, A., Hoang, C. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3909 · Cited by 3,097 · see citing works
Trastuzumab — Mechanism of Action and Use in Clinical Practice
Hudis, C. A. (2007) · New England Journal of Medicine · doi:10.1056/nejmra043186 · Cited by 2,592 · see citing works
T cell exclusion, immune privilege, and the tumor microenvironment
Joyce, J. A., & Fearon, D. T. (2015) · Science · doi:10.1126/science.aaa6204 · Cited by 2,494 · see citing works
Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345 · see citing works
Park, S.-M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008) · Genes & Development · doi:10.1101/gad.1640608 · Cited by 2,272 · see citing works
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes
Cristescu, R., Lee, J., Nebozhyn, M., Kim, K.-M., Ting, J. C., Wong, S. S., Liu, J., Yue, Y. G., Wang, J., Yu, K., et al. (2015) · Nature Medicine · doi:10.1038/nm.3850 · Cited by 2,223 · see citing works
Self-citationSingle-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Azizi, E., Carr, A. J., Plitas, G., Cornish, A. E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.060 · Cited by 1,976 · see citing works
Molecular requirements for epithelial–mesenchymal transition during tumor progression
Huber, M. A., Kraut, N., & Beug, H. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.08.001 · Cited by 1,813 · see citing works
Denkert, C., Loibl, S., Noske, A., Roller, M., Müller, B. M., Komor, M., Budczies, J., Darb‐Esfahani, S., Kronenwett, R., Hanusch, C. A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.7370 · Cited by 1,751 · see citing works
Burk, U., Schubert, J., Wellner, U. F., Schmalhofer, O., Vincan, E., Spaderna, S., & Brabletz, T. (2008) · EMBO Reports · doi:10.1038/embor.2008.74 · Cited by 1,722 · see citing works
The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs
Wellner, U. F., Schubert, J., Burk, U., Schmalhofer, O., Zhu, F., Sonntag, A., Waldvogel, B., Vannier, C., Darling, D. S., Hausen, A. Z., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1998 · Cited by 1,686 · see citing works
Korpal, M., Lee, E. S., Hu, G., & Kang, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c800074200 · Cited by 1,642 · see citing works
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Pathiraja, K., Aktan, G., Cheng, J. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.8931 · Cited by 1,477 · see citing works
The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.
Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L. V., Bruyneel, E., Mareel, M., Huylebroeck, D., & van Roy, F. (2001) · Molecules and Cells · doi:10.1016/s1097-2765(01)00260-x · Cited by 1,464 · see citing works
Creighton, C. J., Li, X., Landis, M. D., Dixon, J. M., Neumeister, V. M., Sjolund, A. B., Rimm, D. L., Wong, H. H., Rodriguez, A. A., Herschkowitz, J. I., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905718106 · Cited by 1,414 · see citing works
Self-citationLanger, C. J., Gadgeel, S. M., Borghaei, H., Papadimitrakopoulou, V. A., Patnaik, A., Powell, S. F., Gentzler, R. D., Martins, R. G., Stevenson, J. P., Jalal, S. I., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30498-3 · Cited by 1,404 · see citing works
PD-L1 Expression in Triple-Negative Breast Cancer
Mittendorf, E. A., Philips, A. V., Meric‐Bernstam, F., Qiao, N., Wu, Y., Harrington, S. M., Su, X., Wang, Y., Gonzalez-Angulo, A. M., Akçakanat, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0127 · Cited by 1,394 · see citing works
Tumor-Infiltrating CD8+Lymphocytes Predict Clinical Outcome in Breast Cancer
Mahmoud, S., Paish, E. C., Powe, D. G., Macmillan, R. D., Grainge, M. J., Lee, A. H. S., Ellis, I. O., & Green, A. R. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.5037 · Cited by 1,367 · see citing works
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302 · see citing works
Self-citationActivation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., et al. (2012) · Nature Genetics · doi:10.1038/ng.2330 · Cited by 1,224 · see citing works
Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells
Shimono, Y., Zabala, M., Cho, R. W., Lobo, N. A., Dalerba, P. D., Qian, D., Diehn, M., Liu, H., Panula, S., Chiao, E. T., et al. (2009) · Cell · doi:10.1016/j.cell.2009.07.011 · Cited by 1,205 · see citing works
Bracken, C., Gregory, P. A., Kolesnikoff, N., Bert, A., Wang, J., Shannon, M., & Goodall, G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1942 · Cited by 1,099 · see citing works
Self-citationByers, L. A., Diao, L., Wang, J., Saintigny, P., Girard, L., Peyton, M., Shen, L., Fan, Y., Giri, U., Tumula, P. K., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1558 · Cited by 1,059 · see citing works
Self-citationTaube, J. H., Herschkowitz, J. I., Komurov, K., Zhou, A. Y., Gupta, S. K., Yang, J., Hartwell, K. A., Önder, T. T., Gupta, P. B., Evans, K. W., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004900107 · Cited by 1,041 · see citing works
Self-citationTGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression
Yang, L., Pang, Y., & Moses, H. L. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.04.002 · Cited by 1,023 · see citing works
Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y., Byers, L. A., Zhang, X., Yi, X., Dwyer, D. W., Lin, W., et al. (2014) · Nature Communications · doi:10.1038/ncomms6241 · Cited by 972 · see citing works
Self-citationClinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890 · see citing works
Zitvogel, L., Galluzzi, L., Smyth, M. J., & Kroemer, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.014 · Cited by 879 · see citing works
Breast Cancer Immunotherapy: Facts and Hopes
Emens, L. A. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3001 · Cited by 876 · see citing works
Bottino, C., Castriconi, R., Pende, D., Rivera, P., Nanni, M., Carnemolla, B., Cantoni, C., Grassi, J., Marcenaro, S., Reymond, N., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030788 · Cited by 874 · see citing works
Acquired resistance to TKIs in solid tumours: learning from lung cancer
Camidge, D. R., Pao, W., & Sequist, L. V. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.104 · Cited by 862 · see citing works
Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function
Condamine, T., & Gabrilovich, D. I. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.10.002 · Cited by 846 · see citing works
Eger, A., Aigner, K., Sonderegger, S., Dampier, B., Oehler, S., Schreiber, M., Berx, G., Cano, A., Beug, H., & Foisner, R. (2005) · Oncogene · doi:10.1038/sj.onc.1208429 · Cited by 808 · see citing works
Adams, S., Schmid, P., Rugo, H. S., Winer, E. P., Loirat, D., Awada, A., Cescon, D. W., Iwata, H., Campone, M., Nanda, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy517 · Cited by 807 · see citing works
Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment
Kim, J., & Bae, J. (2016) · Mediators of Inflammation · doi:10.1155/2016/6058147 · Cited by 803 · see citing works
Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients
Ali, H. R., Provenzano, E., Dawson, S., Blows, F. M., Liu, B., Shah, M., Earl, H. M., Poole, C. J., Hiller, L., Dunn, J., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu191 · Cited by 773 · see citing works
Dirix, L. Y., Takács, I., Jérusalem, G., Nikolinakos, P. G., Arkenau, H., Forero, A., Boccia, R. V., Lippman, M. E., Somer, R. A., Šmakal, M., et al. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4537-5 · Cited by 748 · see citing works
Precision Diagnosis and Treatment for Advanced Non–Small-Cell Lung Cancer
Reck, M., & Rabe, K. F. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1703413 · Cited by 725 · see citing works
Kim, K., Skora, A. D., Li, Z., Liu, Q., Tam, A. J., Blosser, R. L., Diaz, L. A., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410626111 · Cited by 676 · see citing works
A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer
Farmer, P. J., Bonnefoi, H. R., Anderle, P., Cameron, D., Wirapati, P., Becette, V., André, S., Piccart, M. J., Campone, M., Brain, E. G. C., et al. (2009) · Nature Medicine · doi:10.1038/nm.1908 · Cited by 618 · see citing works
Mani, S. A., Yang, J., Brooks, M. W., Schwaninger, G., Zhou, A. Y., Miura, N., Kutok, J. L., Hartwell, K. A., Richardson, A. L., & Weinberg, R. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703900104 · Cited by 576 · see citing works
Self-citationLoi, S., Dushyanthen, S., Beavis, P. A., Salgado, R., Denkert, C., Savas, P., Combs, S., Rimm, D. L., Giltnane, J. M., Estrada, M. V., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1125 · Cited by 536 · see citing works
Mak, M. P., Tong, P., Diao, L., Cardnell, R. J., Gibbons, D. L., William, W. N., Skoulidis, F., Parra, E. R., Rodriguez‐Canales, J., Wistuba, I. I., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0876 · Cited by 526 · see citing works
Self-citationGibbons, D. L., Lin, W., Creighton, C. J., Rizvi, Z. H., Gregory, P. A., Goodall, G. J., Thilaganathan, N., Du, L., Zhang, Y., Pertsemlidis, A., et al. (2009) · Genes & Development · doi:10.1101/gad.1820209 · Cited by 516 · see citing works
Self-citationMicroRNAs as regulators of epithelial-mesenchymal transition
Gregory, P. A., Bracken, C. P., Bert, A. G., & Goodall, G. J. (2008) · Cell Cycle · doi:10.4161/cc.7.20.6851 · Cited by 506 · see citing works
Andersen, M. H., Schrama, D., Straten, P. T., & Becker, J. C. (2005) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700001 · Cited by 492 · see citing works
Teschendorff, A. E., Miremadi, A., Pinder, S. E., Ellis, I. O., & Caldas, C. (2007) · Genome biology · doi:10.1186/gb-2007-8-8-r157 · Cited by 492 · see citing works
Rody, A., Holtrich, U., Pusztai, L., Liedtke, C., Gaetje, R., Ruckhaeberle, E., Solbach, C., Hanker, L., Ahr, A., Metzler, D., et al. (2009) · Breast Cancer Research · doi:10.1186/bcr2234 · Cited by 460 · see citing works
Lou, Y., Diao, L., Parra, E. R., Denning, W. L., Chen, L., Fan, Y. H., Byers, L. A., Wang, J., Papadimitrakopoulou, V. A., Behrens, C., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1434 · Cited by 439 · see citing works
Self-citationLiu, S., Lachapelle, J., Leung, S. C. Y., Gao, D., Foulkes, W. D., & Nielsen, T. O. (2012) · Breast Cancer Research · doi:10.1186/bcr3148 · Cited by 437 · see citing works
New insights into the role of <scp>EMT</scp> in tumor immune escape
Terry, S., Savagner, P., Ortiz‐Cuaran, S., Mahjoubi, L., Saintigny, P., Thiery, J., & Chouaib, S. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12093 · Cited by 414 · see citing works
Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing
Casasent, A. K., Schalck, A., Gao, R., Sei, E., Long, A., Pangburn, W., Casasent, T., Meric-Bernstam, F., Edgerton, M. E., & Navin, N. E. (2018) · Cell · doi:10.1016/j.cell.2017.12.007 · Cited by 411 · see citing works
Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas
Dongre, A., Rashidian, M., Reinhardt, F., Bagnato, A., Keckesova, Z., Ploegh, H. L., & Weinberg, R. A. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3292 · Cited by 395 · see citing works
Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression
Xu, C., Brainson, C. F., Koyama, S., Wu, H., Zhao, Y., Chen, Z., Herter-Sprie, G. S., Akbay, E. A., Tchaicha, J. H., Altabef, A. B., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.033 · Cited by 394 · see citing works
Immunogenic effects of chemotherapy-induced tumor cell death
Wang, Y., Fletcher, R., Yu, J., & Zhang, L. (2018) · Genes & Diseases · doi:10.1016/j.gendis.2018.05.003 · Cited by 316 · see citing works
Dong, P., Xiong, Y., Yue, J., Hanley, S. J. B., & Watari, H. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00386 · Cited by 312 · see citing works
A MicroRNA Expression Signature for Cervical Cancer Prognosis
Hu, X., Schwarz, J. K., Lewis, J. S., Huettner, P. C., Rader, J. S., Deasy, J. O., Grigsby, P. W., & Wang, X. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3289 · Cited by 310 · see citing works
Ceppi, P., Mudduluru, G., Kumarswamy, R., Rapa, I., Scagliotti, G. V., Papotti, M. G., & Allgayer, H. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0052 · Cited by 304 · see citing works
Akalay, I., Janji, B., Hasmim, M., Noman, M. Z., André, F., de Crémoux, P., Bertheau, P., Badoual, C., Vielh, P. R., Larsen, A. K., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2432 · Cited by 302 · see citing works
Iglesia, M. D., Vincent, B. G., Parker, J. S., Hoadley, K. A., Carey, L., Perou, C. M., & Serody, J. S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3368 · Cited by 276 · see citing works
Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab
Brand, T. M., Iida, M., & Wheeler, D. L. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.9.15050 · Cited by 275 · see citing works
Chae, Y. K., Chang, S., Ko, T., Anker, J. F., Agte, S., Iams, W. T., Choi, W. M., Lee, K., & Cruz, M. R. D. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-21061-1 · Cited by 252 · see citing works
Greifenberg, V., Ribechini, E., Rößner, S., & Lutz, M. B. (2009) · European Journal of Immunology · doi:10.1002/eji.200939486 · Cited by 241 · see citing works
Survival Outcomes in Cancer Patients Predicted by a Partial EMT Gene Expression Scoring Metric
George, J. T., Jolly, M. K., Xu, S., Somarelli, J. A., & Levine, H. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3521 · Cited by 240 · see citing works
García-Martínez, E., Gil, G. L., Benito, A. C., González-Billalabeitia, E., Conesa, M. V., García, T., García-Garre, E., Vicente, V., & de la Peña, F. A. (2014) · Breast Cancer Research · doi:10.1186/s13058-014-0488-5 · Cited by 236 · see citing works
Stewart, C. A., Tong, P., Cardnell, R. J., Sen, T., Li, L., Gay, C. M., Masrorpour, F., Fan, Y. H., Bara, R. O., Feng, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15338 · Cited by 227 · see citing works
Self-citationSvoronos, N., Perales‐Puchalt, A., Allegrezza, M. J., Rutkowski, M. R., Payne, K. K., Tesone, A. J., Nguyen, J. M., Curiel, T. J., Cadungog, M. G., Singhal, S. K., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0502 · Cited by 218 · see citing works
Dine, J. L., Gordon, R., Shames, Y., Kasler, M. K., & Barton‐Burke, M. (2017) · Asia-Pacific Journal of Oncology Nursing · doi:10.4103/apjon.apjon_4_17 · Cited by 217 · see citing works
Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation
Welte, T., Kim, I. S., Tian, L. H., Gao, X., Wang, H., Li, J., Holdman, X. B., Herschkowitz, J. I., Pond, A. C., Xie, G., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3355 · Cited by 214 · see citing works
Self-citationPerez, E. A., Thompson, E. A., Ballman, K. V., Anderson, S. K., Asmann, Y. W., Kalari, K. R., Eckel‐Passow, J. E., Dueck, A. C., Tenner, K., Jen, J., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.6298 · Cited by 203 · see citing works
Expression of PD-L1 and prognosis in breast cancer: a meta-analysis
Zhang, M., Sun, H., Zhao, S., Wang, Y., Pu, H., Wang, Y., & Zhang, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.15532 · Cited by 201 · see citing works
Asgarova, A., Asgarov, K., Godet, Y., Peixoto, P., Nadaradjane, A., Boyer‐Guittaut, M., Galaine, J., Guenat, D., Mougey, V., Perrard, J., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2017.1423170 · Cited by 198 · see citing works
Yang, Y., Ahn, Y., Gibbons, D. L., Zang, Y., Lin, W., Thilaganathan, N., Alvarez, C. A., Moreira, D. C., Creighton, C. J., Gregory, P. A., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci42579 · Cited by 196 · see citing works
Self-citationSethi, S. N., Macoska, J. A., Chen, W., & Sarkar, F. H. (2010) · PubMed Central · Cited by 192 · see citing works
Twist1 Induces CCL2 and Recruits Macrophages to Promote Angiogenesis
Low-Marchelli, J. M., Ardi, V. C., Vizcarra, E. A., van Rooijen, N., Quigley, J. P., & Yang, J. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-0653 · Cited by 192 · see citing works
Hsu, D. S., Wang, H.-J., Tai, S., Chou, C.-H., Hsieh, C.-H., Chiu, P.-H., Chen, N., & Yang, M. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.002 · Cited by 191 · see citing works
Baj, J., Korona‐Głowniak, I., Forma, A., Maani, A., Sitarz, R., Rahnama, M., Radzikowska, E., & Portincasa, P. (2020) · Cells · doi:10.3390/cells9041055 · Cited by 173 · see citing works
Forero, A., Li, Y., Chen, D., Grizzle, W. E., Updike, K. L., Merz, N. D., Downs-Kelly, E. P., Burwell, T. C., Vaklavas, C., Buchsbaum, D. J., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0243 · Cited by 170 · see citing works
Ascierto, M. L., Kmieciak, M., Idowu, M. O., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1470-x · Cited by 167 · see citing works
Kim, S., Koh, J., Kim, M., Kwon, D., Go, H., Kim, Y. A., Jeon, Y. K., & Chung, D. H. (2016) · Human Pathology · doi:10.1016/j.humpath.2016.07.007 · Cited by 166 · see citing works
ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression
Ahn, Y., Gibbons, D. L., Chakravarti, D., Creighton, C. J., Rizvi, Z. H., Adams, H. P., Pertsemlidis, A., Gregory, P. A., Wright, J. A., Goodall, G. J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63608 · Cited by 157 · see citing works
Self-citationHernández, L., Wilkerson, P. M., Lambros, M. B. K., et al. (2012) · The Journal of Pathology · doi:10.1002/path.3990 · Cited by 151 · see citing works
Chockley, P. J., Chen, J., Chen, G., Beer, D. G., Standiford, T. J., & Keshamouni, V. G. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97611 · Cited by 140 · see citing works
Immunoediting of Cancers May Lead to Epithelial to Mesenchymal Transition
Knutson, K. L., Lu, H., Stone, B. C., Reiman, J. M., Behrens, M. D., Prosperi, C., Gad, E. A., Smorlesi, A., & Disis, M. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1526 · Cited by 136 · see citing works
Schliekelman, M. J., Gibbons, D. L., Faça, V. M., Creighton, C. J., Rizvi, Z. H., Zhang, Q. H., Wong, C., Wang, H., Ungewiss, C., Ahn, Y., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0964 · Cited by 136 · see citing works
Self-citationCheng, W., Kandel, J. J., Yamashiro, D. J., Canoll, P., & Anastassiou, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034705 · Cited by 132 · see citing works
Adams, S., Schmid, P., Rugo, H. S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.1008 · Cited by 130 · see citing works
Mahic, M., Henjum, K., Yaqub, S., Bjørnbeth, B. A., Torgersen, K. M., Taskén, K., & Aandahl, E. M. (2008) · European Journal of Immunology · doi:10.1002/eji.200737529 · Cited by 124 · see citing works
Triple negative breast cancer – prognostic role of immune-related factors: a systematic review
Stovgaard, E. S., Nielsen, D. L., Høgdall, E. V. S., & Balslev, E. (2017) · Acta Oncologica · doi:10.1080/0284186x.2017.1400180 · Cited by 121 · see citing works
Li, Y., Hofmann, M., Wang, Q., Teng, L., Chlewicki, L. K., Pircher, H., & Mariuzza, R. A. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.019 · Cited by 115 · see citing works
Fardi, M., Alivand, M. R., Baradaran, B., Hagh, M. F., & Solali, S. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28277 · Cited by 114 · see citing works
Prospects for new lung cancer treatments that target EMT signaling
Otsuki, Y., Saya, H., & Arima, Y. (2017) · Developmental Dynamics · doi:10.1002/dvdy.24596 · Cited by 112 · see citing works
The role of CD8 T cells in innate immunity and in antigen non-specific protection
Berg, R. E., & Forman, J. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.03.010 · Cited by 109 · see citing works
Ascierto, M. L., Idowu, M. O., Zhao, Y., Khalak, H. G., Payne, K. K., Wang, X., Dumur, C. I., Bedognetti, D., Tomei, S., Ascierto, P. A., et al. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-145 · Cited by 108 · see citing works
The Role of MicroRNAs in Breast Cancer Stem Cells
Schwarzenbacher, D., Balić, M., & Pichler, M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140714712 · Cited by 81 · see citing works
Zhang, L., Liang, Y., Li, S., Zeng, F., Meng, Y., Chen, Z., Liu, S., Tao, Y., & Yu, F. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0989-z · Cited by 73 · see citing works
Macrophages promote the progression of premalignant mammary lesions to invasive cancer
Carron, E. C., Homra, S., Rosenberg, J. N., Coffelt, S. B., Kittrell, F. S., Zhang, Y., Creighton, C. J., Fuqua, S. A. W., Medina, D., & Machado, H. L. (2017) · Oncotarget · doi:10.18632/oncotarget.14913 · Cited by 72 · see citing works
Ungewiss, C., Rizvi, Z. H., Roybal, J. D., Peng, D. H., Gold, K. A., Shin, D. H., Creighton, C. J., & Gibbons, D. L. (2016) · Scientific Reports · doi:10.1038/srep18652 · Cited by 70 · see citing works
Self-citationTargeting the programmed cell death-1 pathway in breast and ovarian cancer
Emens, L. A., Kok, M., & Ojalvo, L. S. (2016) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000257 · Cited by 58 · see citing works
TGF β : A player on multiple fronts in the tumor microenvironment
Čaja, F., & Vannucci, L. E. (2014) · Journal of Immunotoxicology · doi:10.3109/1547691x.2014.945667 · Cited by 56 · see citing works
Markiewicz, A., Topa, J., Nagel, A. C., Skokowski, J., Seroczyńska, B., Stokowy, T., Wełnicka-Jaśkiewicz, M., & Zaczek, A. J. (2019) · Cancers · doi:10.3390/cancers11010059 · Cited by 55 · see citing works
Tumor Plasticity Interferes with Anti-Tumor Immunity
Chouaı̈b, S., Janji, B., Tittarelli, A., Eggermont, A. M. M., & Thiery, J. P. (2014) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2014010183 · Cited by 50 · see citing works
Dual role of immunomodulation by anticancer chemotherapy
Shurin, M. R. (2013) · Nature Medicine · doi:10.1038/nm.3045 · Cited by 47 · see citing works
Targeting CD8 + T-cell Tolerance for Cancer Immunotherapy
Jackson, S. R., Yuan, J., & Teague, R. M. (2014) · Immunotherapy · doi:10.2217/imt.14.51 · Cited by 47 · see citing works
Ramani, V. C., Lemaire, C. A., Triboulet, M. M., et al. (2019) · Breast Cancer Research · doi:10.1186/s13058-019-1182-4 · Cited by 47 · see citing works
McArthur, H. L., & Page, D. B. (2016) · PubMed · Cited by 46 · see citing works
Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS
Sugio, T., Miyawaki, K., Kato, K., Sasaki, K., Yamada, K., Iqbal, J., Miyamoto, T., Ohshima, K., Maeda, T., Miyoshi, H., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2018018754 · Cited by 46 · see citing works
Kumar, S., Davra, V., Obr, A. E., Geng, K., Wood, T. L., Lorenzo, M. S. D., & Birge, R. B. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1376155 · Cited by 44 · see citing works
Zhang, Z., Liu, L., Cao, S., Zhu, Y. Z., & Mei, Q. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.03.007 · Cited by 36 · see citing works
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., & Liang, L. (2018) · Oncology Reports · doi:10.3892/or.2018.6474 · Cited by 33 · see citing works
Self-citationSIGNATURE: A workbench for gene expression signature analysis
Chang, J. T., Gatza, M. L., Lucas, J. E., Barry, W. T., Vaughn, P., & Nevins, J. R. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-443 · Cited by 32 · see citing works
Self-citationNiyomnaitham, S., Parinyanitikul, N., Roothumnong, E., Jinda, W., Samarnthai, N., Atikankul, T., Suktitipat, B., Thongnoppakhun, W., Limwongse, C., & Pithukpakorn, M. (2019) · PeerJ · doi:10.7717/peerj.6501 · Cited by 31 · see citing works
A New Strategy Using ALDHhigh-CD8+T Cells to Inhibit Tumorigenesis
Luo, H., Zeng, C., Fang, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103193 · Cited by 30 · see citing works
Matteis, S. D., Canale, M., Verlicchi, A., Bronte, G., Delmonte, A., Crinò, L., Martinelli, G., & Ulivi, P. (2019) · Journal of Oncology · doi:10.1155/2019/7475364 · Cited by 27 · see citing works
Repurposing Antiestrogens for Tumor Immunotherapy
Welte, T., Zhang, X. H.-F., & Rosen, J. M. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1308 · Cited by 25 · see citing works
Self-citationLee, H. W., Cho, H.-H., Joung, J., Jeon, H. G., Jeong, B. C., Jeon, S. S., Lee, H. M., Nam, D., Park, W., Kim, C. K., et al. (2020) · Cancers · doi:10.3390/cancers12040866 · Cited by 25 · see citing works
Terry, S., & Chouaı̈b, S. (2015) · Oncoscience · doi:10.18632/oncoscience.226 · Cited by 23 · see citing works
Dye, E. S. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.4.1510 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Luo, F., Lu, F.-T., Cao, J.-X., Ma, W.-J., Xia, Z.-F., Zhan, J.-H., Zeng, K.-M., Huang, Y., Zhao, H.-Y., & Zhang, L. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.01.027 · Cited by 95 · see citing works
- Authors
- Soundararajan, R., Fradette, J., Konen, J., Moulder, S., Zhang, X., Gibbons, D., Varadarajan, N., Wistuba, I., Tripathy, D., Bernatchez, C., Byers, L., Chang, J., Contreras, A., Lim, B., Parra, E., Roarty, E., Wang, J., Yang, F., Barton, M., Rosen, J., & Mani, S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- University of Houston (US)
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Rosen, Jeffrey
- Mani, Sendurai
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2019-05-24
- Volume
- 11
- Issue
- 5
- Pages
- 714
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC6562947
- OpenAlex
- W2945884255
- Cited by
- 103
- References
- 139
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 22 · 2021: 25 · 2020: 24 · 2019: 4
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (2R01CA155243, NIH R37 CA214609-01A1)
- NIH/NCI CCSG (P30-CA01667)
- NIH/NCI SPORE (P5-CA070907)
- MD Andersen Cancer Center Physician Scientist Award (N/A)
- LUNGevity Foundation (N/A)
- philanthropic contributions to The University of Texas MD Anderson Cancer Center Lung Cancer Moonshot Program (N/A)
- CPRIT-MIRA (RP160652-P3, RP160710, RP180712)
- Rexanna’s Foundation for Fighting Lung Cancer (N/A)
- UT Lung SPORE Career Enhancement Award (P50 CA070907)
- NIH/NCI (R01CA200970)
- National Science Foundation (15-597-1605817)
- CPRIT-IIRA (RP170172)
- Dana Helis Henry and Andrienne Helis Malvin Medical Research Foundation Grant (N/A)
- National Cancer Institute - University of Texas MD Anderson Prostate Cancer SPORE Career Enhancement Program Award (P50 CA140388)
- MD Anderson Institutional Research Grant (N/A)
- CPRIT (RP180466)
- MRA (509800)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- epithelial-mesenchymal transition, cancer immunotherapy, immune checkpoint inhibitors, treatment resistance, non-small cell lung cancer, triple-negative breast cancer, tumor immunosuppression, tumor microenvironment, metastasis, cancer stemness, combination therapy, chemoresistance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review