Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells
Open accessAbstract
Our bodies are equipped with powerful immune surveillance to clear cancerous cells as they emerge. How tumor-initiating stem cells (tSCs) that form and propagate cancers equip themselves to overcome this barrier remains poorly understood. To tackle this problem, we designed a skin cancer model for squamous cell carcinoma (SCC) that can be effectively challenged by adoptive cytotoxic T cell transfer (ACT)-based immunotherapy. Using single-cell RNA sequencing (RNA-seq) and lineage tracing, we found that transforming growth factor β (TGF-β)-responding tSCs are superior at resisting ACT and form the root of tumor relapse. Probing mechanism, we discovered that during malignancy, tSCs selectively acquire CD80, a surface ligand previously identified on immune cells. Moreover, upon engaging cytotoxic T lymphocyte antigen-4 (CTLA4), CD80-expressing tSCs directly dampen cytotoxic T cell activity. Conversely, upon CTLA4- or TGF-β-blocking immunotherapies or Cd80 ablation, tSCs become vulnerable, diminishing tumor relapse after ACT treatment. Our findings place tSCs at the crux of how immune checkpoint pathways are activated.
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TSKs resemble tumor-initiating stem cells better equipped to survive adoptive cytotoxic T cell therapy in a mouse model of cSCC.
“The latter possibility is consistent with TSKs resembling tumor-initiating stem cells better equipped to survive adoptive cytotoxic T cell therapy in a mouse model of cSCC (Miao et al., 2019).”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Miao et al., 2019
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Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400 · 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
Model-Based Clustering, Discriminant Analysis, and Density Estimation
Fraley, C., & Raftery, A. E. (2002) · Journal of the American Statistical Association · doi:10.1198/016214502760047131 · Cited by 4,274 · see citing works
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137 · see citing works
Cancer immunotherapy comes of age
Mellman, I., Coukos, G., & Dranoff, G. (2011) · Nature · doi:10.1038/nature10673 · Cited by 3,893 · see citing works
Batlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769 · see citing works
Evolution of the Cancer Stem Cell Model
Kreso, A., & Dick, J. E. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.006 · Cited by 2,212 · see citing works
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
Platt, R. J., Chen, S., Zhou, Y., Yim, M. J., Swiech, L., Kempton, H. R., Dahlman, J. E., Parnas, O., Eisenhaure, T. M., Jovanovic, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.014 · Cited by 2,001 · see citing works
TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis
Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., et al. (2018) · Nature · doi:10.1038/nature25492 · Cited by 1,851 · see citing works
Adoptive immunotherapy for cancer: harnessing the T cell response
Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012) · Nature Reviews Immunology · doi:10.1038/nri3191 · Cited by 1,688 · see citing works
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
Tran, E., Robbins, P. F., Lu, Y.-C., Prickett, T. D., Gartner, J. J., Jia, L., Pasetto, A., Zheng, Z., Ray, S., Groh, E. M., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1609279 · Cited by 1,368 · see citing works
Natural selection of tumor variants in the generation of “tumor escape” phenotypes
Khong, H. T., & Restifo, N. P. (2002) · Nature Immunology · doi:10.1038/ni1102-999 · Cited by 1,058 · see citing works
Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties
Schwitalla, S., Fingerle, A. A., Cammareri, P., Nebelsiek, T., Göktuna, S. İ., Ziegler, P. K., Canli, Ö., Heijmans, J., Huels, D. J., Moreaux, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.12.012 · Cited by 1,057 · see citing works
Notch1 functions as a tumor suppressor in mouse skin
Nicolas, M., Wolfer, A., Raj, K., Kummer, J. A., Mill, P., van Noort, M., Hui, C., Clevers, H. C., Dotto, G. P., & Radtke, F. (2003) · Nature Genetics · doi:10.1038/ng1099 · Cited by 969 · see citing works
Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082492 · Cited by 967 · see citing works
Essential role for oncogenic Ras in tumour maintenance
Chin, L., Tam, A., Pomerantz, J. H., Wong, M., Holash, J., Bardeesy, N., Shen, Q., O'Hagan, R., Pantginis, J., Zhou, H., et al. (1999) · Nature · doi:10.1038/22788 · Cited by 928 · see citing works
T-cell regulation by CD28 and CTLA-4
Alegre, M., Frauwirth, K. A., & Thompson, C. B. (2001) · Nature reviews. Immunology · doi:10.1038/35105024 · Cited by 912 · see citing works
Carreno, B. M., & Collins, M. A. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.091101.091806 · Cited by 895 · see citing works
TGF-β Activation and Function in Immunity
Travis, M. A., & Sheppard, D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120257 · Cited by 856 · see citing works
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses
Walker, L. S. K., & Sansom, D. M. (2011) · Nature reviews. Immunology · doi:10.1038/nri3108 · Cited by 786 · see citing works
SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma
Boumahdi, S., Driessens, G., Lapouge, G., Rorive, S., Nassar, D., Mercier, M. L., Delatte, B., Caauwe, A., Lenglez, S., Nkusi, E., et al. (2014) · Nature · doi:10.1038/nature13305 · Cited by 657 · see citing works
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation
Landsberg, J., Sirokay, J. D., Renn, M., Bald, T., Rogava, M., Cron, M., Fatho, M., Lennerz, V., Wölfel, T., Hölzel, M., et al. (2012) · Nature · doi:10.1038/nature11538 · Cited by 635 · see citing works
TGF-β Tumor Suppression through a Lethal EMT
David, C. J., Huang, Y.-H., Chen, M., Su, J., Zou, Y., Bardeesy, N. M., Iacobuzio–Donahue, C. A., & Massagué, J. (2016) · Cell · doi:10.1016/j.cell.2016.01.009 · Cited by 597 · see citing works
CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics
van der Merwe, P. A., Bodian, D. L., Daenke, S., Linsley, P., & Davis, S. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.393 · Cited by 551 · see citing works
Expression of tumour-specific antigens underlies cancer immunoediting
DuPage, M. J. P., Mazumdar, C., Schmidt, L., Cheung, A. F., & Jacks, T. (2012) · Nature · doi:10.1038/nature10803 · Cited by 529 · see citing works
TGF-β Promotes Heterogeneity and Drug Resistance in Squamous Cell Carcinoma
Oshimori, N., Oristian, D., & Fuchs, E. (2015) · Cell · doi:10.1016/j.cell.2015.01.043 · Cited by 471 · see citing works
Self-citationA vascular niche and a VEGF–Nrp1 loop regulate the initiation and stemness of skin tumours
Beck, B., Driessens, G., Goossens, S., Youssef, K. K., Kuchnio, A., Caauwe, A., Sotiropoulou, P. A., Loges, S., Lapouge, G., Candi, A., et al. (2011) · Nature · doi:10.1038/nature10525 · Cited by 466 · see citing works
A model for RAS mutation patterns in cancers: finding the sweet spot
Li, S., Balmain, A., & Counter, C. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0076-6 · Cited by 384 · see citing works
Mackensen, A., Meidenbauer, N., Vogl, S., Laumer, M., Berger, J., & Andreesen, R. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.1100 · Cited by 297 · see citing works
Identifying the cellular origin of squamous skin tumors
Lapouge, G., Youssef, K. K., Vokaer, B., Achouri, Y., Michaux, C., Sotiropoulou, P. A., & Blanpain, C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012720108 · Cited by 294 · see citing works
Response to self antigen imprints regulatory memory in tissues
Rosenblum, M. D., Gratz, I. K., Paw, J. S., Lee, K., Marshak‐Rothstein, A., & Abbas, A. K. (2011) · Nature · doi:10.1038/nature10664 · Cited by 281 · see citing works
Self-citationDirect in Vivo RNAi Screen Unveils Myosin IIa as a Tumor Suppressor of Squamous Cell Carcinomas
Schramek, D., Sendoel, A., Segal, J. P., Beronja, S., Heller, E., Oristian, D., Reva, B. A., & Fuchs, E. V. (2014) · Science · doi:10.1126/science.1248627 · Cited by 269 · see citing works
Self-citationBremner, R., & Balmain, A. (1990) · Cell · doi:10.1016/0092-8674(90)90523-h · Cited by 264 · see citing works
Schöber, M., & Fuchs, E. V. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107807108 · Cited by 261 · see citing works
Self-citationQuiescent tissue stem cells evade immune surveillance
Agudo, J., Park, E. S., Rose, S. A., Alibo, E., Sweeney, R., Dhainaut, M., Kobayashi, K. S., Sachidanandam, R., Baccarini, A., Merad, M., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.02.001 · Cited by 244 · see citing works
Beronja, S., Livshits, G., Williams, S. E., & Fuchs, E. V. (2010) · Nature Medicine · doi:10.1038/nm.2167 · Cited by 209 · see citing works
Self-citationAn obligate cell-intrinsic function for CD28 in Tregs
Zhang, R., Huynh, A., Whitcher, G. H., Chang, J., Maltzman, J. S., & Turka, L. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65013 · Cited by 208 · see citing works
Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma
Nassar, D., Latil, M., Boeckx, B., Lambrechts, D., & Blanpain, C. (2015) · Nature Medicine · doi:10.1038/nm.3878 · Cited by 185 · see citing works
Defining the origins of Ras/p53-mediated squamous cell carcinoma
White, A. C., Tran, K. V., Khuu, J., Dang, C., Cui, Y., Binder, S. W., & Lowry, W. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012670108 · Cited by 185 · see citing works
PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface
Chaudhri, A., Xiao, Y., Klee, A. N., Wang, X., Zhu, B., & Freeman, G. J. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0316 · Cited by 177 · see citing works
RNAi screens in mice identify physiological regulators of oncogenic growth
Beronja, S., Janki, P., Heller, E., Lien, W., Keyes, B. E., Oshimori, N., & Fuchs, E. V. (2013) · Nature · doi:10.1038/nature12464 · Cited by 162 · see citing works
Self-citationBrown, J. A., Yonekubo, Y., Hanson, N. C., Sastre-Perona, A., Basin, A., Rytlewski, J. A., Dolgalev, I., Meehan, S. A., Tsirigos, A., Beronja, S., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.10.001 · Cited by 161 · see citing works
TGF-β Inhibition and Immunotherapy: Checkmate
Ganesh, K., & Massagué, J. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.037 · Cited by 125 · see citing works
Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness
Lapouge, G., Beck, B., Nassar, D., Dubois, C., Dekoninck, S., & Blanpain, C. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.312 · Cited by 81 · see citing works
Yang, H., Schramek, D., Adam, R. C., Keyes, B. E., Wang, P., Zheng, D., & Fuchs, E. V. (2015) · eLife · doi:10.7554/elife.10870 · Cited by 77 · see citing works
Self-citationPapotto, P. H., Marengo, E. B., Sardinha, L. R., Carvalho, K. I., de Carvalho, A. E. Z., Castillo-Méndez, S. I., Jank, C. C., Vanhove, B., Goldberg, A. C., & Rizzo, L. V. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171822 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Tumour-intrinsic resistance to immune checkpoint blockade
Kalbasi, A. K., & Ribas, A. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0218-4 · Cited by 1,491 · see citing works
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117 · see citing works
“The latter possibility is consistent with TSKs resembling tumor-initiating stem cells better equipped to survive adoptive cytotoxic T cell therapy in a mouse model of cSCC (Miao et al., 2019).”
ResultIntratumoral heterogeneity in cancer progression and response to immunotherapy
Vitale, I., Shema, E., Loi, S., & Galluzzi, L. (2021) · Nature Medicine · doi:10.1038/s41591-021-01233-9 · Cited by 823 · see citing works
Clara, J., Monge, C., Yang, Y., & Takebe, N. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0293-2 · Cited by 752 · see citing works
Cancer stem cell–immune cell crosstalk in tumour progression
Bayık, D., & Lathia, J. D. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00366-w · Cited by 563 · see citing works
Identifying phenotype-associated subpopulations by integrating bulk and single-cell sequencing data
Sun, D., Guan, X., Moran, A. E., Wu, L., Qian, D. Z., Schedin, P. S., Dai, M., Danilov, A. V., Alumkal, J. J., Adey, A., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01091-3 · Cited by 511 · see citing works
A single-cell landscape of high-grade serous ovarian cancer
Izar, B., Tirosh, I., Stover, E. H., Wakiro, I., Cuoco, M. S., Alter, I., Rodman, C., Leeson, R. L., Su, M.-J., Shah, P., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0926-0 · Cited by 508 · see citing works
Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant
Yang, C. Q., Xia, B.-R., Zhang, Z.-C., Zhang, Y., Lou, G., & Jin, W. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.577869 · Cited by 354 · see citing works
Cancer cell plasticity during tumor progression, metastasis and response to therapy
Pérez-González, A., Bévant, K., & Blanpain, C. (2023) · Nature Cancer · doi:10.1038/s43018-023-00595-y · Cited by 353 · see citing works
Loh, J.-J., & Ma, S. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.04.004 · Cited by 327 · see citing works
CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance
Wang, C., Li, Y., Jia, L., Kim, J. K., Li, J., Deng, P., Zhang, W., Krebsbach, P. H., & Wang, C. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.04.011 · Cited by 314 · see citing works
Persistent Cancer Cells: The Deadly Survivors
Shen, S., Vagner, S., & Robert, C. (2020) · Cell · doi:10.1016/j.cell.2020.10.027 · Cited by 304 · see citing works
Applications of Surface Modification Technologies in Nanomedicine for Deep Tumor Penetration
Li, Z., Shan, X., Chen, Z., Gao, N., Zeng, W., Zeng, X., & Mei, L. (2020) · Advanced Science · doi:10.1002/advs.202002589 · Cited by 219 · see citing works
Ma, L., Chen, C., Zhao, C., Li, T., Ma, L., Jiang, J., Duan, Z., Si, Q., Chuang, T., Xiang, R., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01772-w · Cited by 217 · see citing works
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities
Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210 · see citing works
Stem Cell Plasticity and Dormancy in the Development of Cancer Therapy Resistance
Angelis, M. L. D., Francescangeli, F., Torre, F. L., & Zeuner, A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00626 · Cited by 203 · see citing works
Understanding tumour endothelial cell heterogeneity and function from single-cell omics
Zeng, Q., Mousa, M., Nadukkandy, A. S., Franssens, L., Alnaqbi, H., Alshamsi, F., Safar, H. A., & Carmeliet, P. (2023) · Nature Reviews. Cancer · doi:10.1038/s41568-023-00591-5 · Cited by 196 · see citing works
Drug-tolerant persister cells in cancer: the cutting edges and future directions
Pu, Y., Li, L., Peng, H., Liu, L., Heymann, D., Robert, C., Vallette, F. M., & Shen, S. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00815-5 · Cited by 179 · see citing works
Beyond genetics: driving cancer with the tumour microenvironment behind the wheel
Yuan, S., Almagro, J., & Fuchs, E. V. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00660-9 · Cited by 178 · see citing works
Self-citationWu, B., Shi, X., Jiang, M., & Liu, H. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01748-4 · Cited by 173 · see citing works
Xu, K., Wang, R., Xie, H., Hu, L., Wang, C., Xu, J., Zhu, C., Liu, Y., Gao, F., Li, X., et al. (2021) · Oncogenesis · doi:10.1038/s41389-021-00355-6 · Cited by 166 · see citing works
Xie, F., Zhou, X., Su, P., Li, H., Tu, Y., Du, J., Pan, C., Xiang, W. D., Zheng, M., Jin, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31250-2 · Cited by 164 · see citing works
Cancer stem cell mimicry for immune evasion and therapeutic resistance
Saw, P. E., Liu, Q., Wong, P., & Song, E. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.06.003 · Cited by 164 · see citing works
Zhu, P., Lu, T., Chen, Z., Liu, B., Fan, D., Li, C., Wu, J., He, L., Zhu, X., Du, Y., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.04.024 · Cited by 160 · see citing works
Jia, L., Zhang, W., & Wang, C. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.022 · Cited by 158 · see citing works
Stem cell quiescence: the challenging path to activation
Urbán, N., & Cheung, T. H. (2021) · Development · doi:10.1242/dev.165084 · Cited by 154 · see citing works
Valle, S., Alcalá, S., Martín-Hijano, L., Cabezas‐Sainz, P., Navarro, D., Muñoz, E. R., Yuste, L., Tiwary, K., Walter, K., Ruíz-Cañas, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18954-z · Cited by 153 · see citing works
Cui, F., Sun, H., Yang, X., Zhou, H., Wu, Y., Li, J., Li, H., Liu, J., Zeng, C., Qu, B., et al. (2023) · Chemical Engineering Journal · doi:10.1016/j.cej.2023.141303 · Cited by 146 · see citing works
Advances in cutaneous squamous cell carcinoma
Winge, M. C. G., Kellman, L. N., Guo, K., Tang, J. Y., Swetter, S. M., Aasi, S. Z., Sarin, K. Y., Chang, A. L. S., & Khavari, P. A. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00583-5 · Cited by 149 · see citing works
Chen, L., Yang, Q., Li, Y., Yang, L., Liu, J., Li, H., Xiao, Y., Bu, L., Zhang, W., & Sun, Z. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0394 · Cited by 144 · see citing works
Interferons in cancer immunoediting: sculpting metastasis and immunotherapy response
von Locquenghien, M., Rozalén, C., & Celià-Terrassa, T. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143296 · Cited by 144 · see citing works
circFAT1 Promotes Cancer Stemness and Immune Evasion by Promoting STAT3 Activation
Jia, L., Wang, Y., & Wang, C. (2021) · Advanced Science · doi:10.1002/advs.202003376 · Cited by 144 · see citing works
Slow-cycling (dormant) cancer cells in therapy resistance, cancer relapse and metastasis
Basu, S., Yang, D. Y., Kumar, R., Jeter, C. R., & Tang, D. G. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.04.021 · Cited by 142 · see citing works
Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells
Perry, J. M., Fang, T., Roy, A., Lin, T. L., He, X., Chen, S., Lü, X., Nemechek, J. M., Ruan, L., Yu, X., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0507-y · Cited by 137 · see citing works
Wei, F., Wang, D., Wei, J., Tang, N., Tang, L. M., Xiong, F., Guo, C. J., Zhou, M., Li, X., Li, G., et al. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03581-0 · Cited by 128 · see citing works
Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers
Lei, M. M. L., & Lee, T. K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.692940 · Cited by 123 · see citing works
Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B
Musella, M., Guarracino, A., Manduca, N., Galassi, C., Ruggiero, E., Potenza, A., Maccafeo, E., Manic, G., Mattiello, L., Rehim, S. S. A., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01290-3 · Cited by 122 · see citing works
The influence of microenvironment on tumor immunotherapy
Zhang, J., Shi, Z., Xu, X., Yu, Z., & Mi, J. (2019) · FEBS Journal · doi:10.1111/febs.15028 · Cited by 112 · see citing works
Fighting Drug Resistance through the Targeting of Drug-Tolerant Persister Cells
De Conti, G., Dias, M. H., & Bernards, R. (2021) · Cancers · doi:10.3390/cancers13051118 · Cited by 111 · see citing works
Recent progress in tumor photodynamic immunotherapy
Shen, L., Zhou, T., Fan, Y., Chang, X. Y., Wang, Y., Sun, J., Xing, L., & Jiang, H. (2020) · Chinese Chemical Letters · doi:10.1016/j.cclet.2020.02.007 · Cited by 105 · see citing works
Cancer stem cells and niches: challenges in immunotherapy resistance
Pan, Y., Yuan, C., Zeng, C., Sun, C., Xia, L., Wang, G., Chen, X., Zhang, B., Liu, J., & Ding, Z. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02265-2 · Cited by 110 · see citing works
He, C., Yu, L., Yao, H., Chen, Y., & Hao, Y. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202006214 · Cited by 101 · see citing works
Convergent inducers and effectors of T cell paralysis in the tumour microenvironment
Hanahan, D., Michielin, O. A., & Pittet, M. J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00761-z · Cited by 102 · see citing works
Single-cell RNA sequencing in cancer: Applications, advances, and emerging challenges
Sun, G., Li, Z., Rong, D., Zhang, H., Shi, X., Yang, W., Zheng, W., Sun, G., Wu, F., Cao, H., et al. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.04.001 · Cited by 104 · see citing works
The Role of the Microenvironment and Immune System in Regulating Stem Cell Fate in Cancer
Ferguson, L. P., Diaz, E., & Reya, T. (2021) · Trends in cancer · doi:10.1016/j.trecan.2020.12.014 · Cited by 96 · see citing works
Platelet-armored nanoplatform to harmonize janus-faced IFN-γ against tumor recurrence and metastasis
Li, Q., Zhou, Y., He, W., Ren, X., Zhang, M., Jiang, Y., Zhou, Z., & Luan, Y. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.08.020 · Cited by 93 · see citing works
Adult stem cells and regenerative medicine—a symposium report
Cable, J., Fuchs, E. V., Weissman, I. L., Jasper, H., Glass, D. J., Rando, T. A., Blau, H. M., Debnath, S., Oliva, A. A., Park, S., et al. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14243 · Cited by 93 · see citing works
Self-citationOncofetal reprogramming in tumour development and progression
Sharma, A., Blériot, C., Currenti, J., & Ginhoux, F. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00497-8 · Cited by 95 · see citing works
Ras drives malignancy through stem cell crosstalk with the microenvironment
Yuan, S., Stewart, K. S., Yang, Y., Abdusselamoglu, M. D., Parigi, S. M., Feinberg, T. Y., Tumaneng, K., Yang, H., Levorse, J. M., Polak, L., et al. (2022) · Nature · doi:10.1038/s41586-022-05475-6 · Cited by 92 · see citing works
Self-citationHu, B., Xu, Y., Li, Y., Huang, J., Cheng, J., Guo, W., Yin, Y., Gao, Y., Wang, P., Wu, S., et al. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.233 · Cited by 87 · see citing works
Cancer Immunotherapy via Targeting Cancer Stem Cells Using Vaccine Nanodiscs
Najafabadi, A. H., Zhang, J., Aikins, M. E., Najafabadi, Z. I., Liao, F., Qin, Y., Okeke, E. B., Scheetz, L. M., Nam, J., Xu, Y., et al. (2020) · Nano Letters · doi:10.1021/acs.nanolett.0c03414 · Cited by 86 · see citing works
Yamashita, N., Long, M. D., Fushimi, A., Yamamoto, M., Hata, T., Hagiwara, M., Bhattacharya, A., Hu, Q., Wong, K., Liu, S., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002115 · Cited by 83 · see citing works
Chen, Z., Lu, T., Huang, L., Wang, Z., Yan, Z., Guan, Y., Hu, W., Fan, Z., & Zhu, P. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148020 · Cited by 85 · see citing works
Targeting cancer stem cells in squamous cell carcinoma
Chen, D., & Wang, C. (2019) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbz016 · Cited by 81 · see citing works
He, X., Smith, S. E., Chen, S., Li, H., Wu, D., Meneses-Giles, P., Wang, Y., Hembree, M. J., Yi, K., Zhao, X., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109674 · Cited by 79 · see citing works
Anti-PD-1/PD-L1 therapy for colorectal cancer: Clinical implications and future considerations
Chen, X., Chen, L., Peng, X., Deng, L., Wang, Y., Li, J.-J., Guo, D., & Niu, X. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101851 · Cited by 80 · see citing works
Liu, X., Adorno-Cruz, V., Chang, Y.-F., Jia, Y., Kawaguchi, M., Dashzeveg, N. K., Taftaf, R., Ramos, E. K., Schuster, E. J., El-Shennawy, L., et al. (2021) · Theranostics · doi:10.7150/thno.57706 · Cited by 76 · see citing works
Immune evader cancer stem cells direct the perspective approaches to cancer immunotherapy
Dianat‐Moghadam, H., Mahari, A., Salahlou, R., Khalili, M., Azizi, M., & Sadeghzadeh, H. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02829-9 · Cited by 80 · see citing works
ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis
Adorno-Cruz, V., Hoffmann, A. D., Liu, X., Dashzeveg, N. K., Taftaf, R., Wray, B. D., Keri, R. A., & Liu, H. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.01.015 · Cited by 77 · see citing works
Cheng, X., Fan, K., Wang, L., Ying, X., Sanders, A. J., Guo, T., Xing, X., Zhou, M., Du, H., Hu, Y., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2272-z · Cited by 75 · see citing works
Beziaud, L., Young, C. M., Alonso, A. M., Norkin, M., Minafra, A. R., & Huelsken, J. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.05.007 · Cited by 76 · see citing works
Granhøj, J. S., Jensen, A. W. P., Presti, M., Met, Ö., Svane, I. M., & Donia, M. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2064711 · Cited by 74 · see citing works
Risk-associated alterations in marrow T cells in pediatric leukemia
Bailur, J. K., McCachren, S. S., Pendleton, K. E., Vasquez, J. C., Lim, H. S., Duffy, A. M., Doxie, D. B., Kaushal, A., Foster, C., DeRyckere, D., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.140179 · Cited by 73 · see citing works
Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy
Yang, C. G., Geng, H., Yang, X., Ji, S., Liu, Z., Feng, H., Li, Q., Zhang, T., Zhang, S., Ma, X., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.10.008 · Cited by 74 · see citing works
Self-citationDolina, J. S., Lee, J., Brightman, S. E., McArdle, S., Hall, S. M., Thota, R. R., Zavala, K. S., Lanka, M., Premlal, A. L. R., Greenbaum, J., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci164258 · Cited by 68 · see citing works
Pérez-Núñez, I., Rozalén, C., Palomeque, J. Á., Sangrador, I., Dalmau, M., Comerma, L., Hernández-Prat, A., Casadevall, D., Menéndez, S., Liu, D., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00339-4 · Cited by 63 · see citing works
Cancer biology deciphered by single-cell transcriptomic sequencing
Li, Y., Jin, J., & Bai, F. (2021) · Protein & Cell · doi:10.1007/s13238-021-00868-1 · Cited by 67 · see citing works
A Review of the Role of Wnt in Cancer Immunomodulation
Goldsberry, W. N., Londoño, A. I., Randall, T. D., Norian, L. A., & Arend, R. C. (2019) · Cancers · doi:10.3390/cancers11060771 · Cited by 66 · see citing works
Chen, Z., He, Q., Lu, T., Wu, J., Shi, G., He, L., Zong, H., Liu, B., & Zhu, P. (2023) · Nature Communications · doi:10.1038/s41467-023-36651-5 · Cited by 66 · see citing works
Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity
Pan, D., & Jia, D. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.757024 · Cited by 64 · see citing works
He, J., Zhou, Y. L., & Sun, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01438-0 · Cited by 69 · see citing works
Midbrain microglia mediate a specific immunosuppressive response under inflammatory conditions
Abellanas, M. A., Zamarbide, M., Basurco, L., Luquin, E., García‐Granero, M., Clavero, P., Martín‐Úriz, P. S., Vilas‐Zornoza, A., Mengual, E., Hervás‐Stubbs, S., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1628-8 · Cited by 64 · see citing works
Li, C., You, X., Xu, X., Wu, B., Liu, Y., Tong, T., Chen, J., Li, Y., Dai, C., Ye, Z., et al. (2022) · Advanced Science · doi:10.1002/advs.202104134 · Cited by 63 · see citing works
Hargadon, K. M. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.37 · Cited by 61 · see citing works
Miyazaki, T., Chung, S., Sakai, H., Ohata, H., Obata, Y., Shiokawa, D., Mizoguchi, Y., Kubo, T., Ichikawa, H., Taniguchi, H., et al. (2021) · Cancer Science · doi:10.1111/cas.15182 · Cited by 60 · see citing works
Cancer stem cells in immunoregulation and bypassing anti-checkpoint therapy
Rouzbahani, E., Majidpoor, J., Najafi, S., & Mortezaee, K. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113906 · Cited by 62 · see citing works
Chen, K., Shuen, T. W. H., & Chow, P. K. H. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02684-w · Cited by 60 · see citing works
T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity
Canel, M., Taggart, D., Sims, A. H., Lonergan, D. W., Waizenegger, I. C., & Serrels, A. (2020) · eLife · doi:10.7554/elife.48092 · Cited by 58 · see citing works
Greco, R., Qu, H., Qu, H., Theilhaber, J., Shapiro, G., Gregory, R. C., Winter, C. G., Malkova, N. V., Sun, F. F., Jaworski, J. A., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1811605 · Cited by 58 · see citing works
The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine
Li, X., Li, M., Huang, M., Lin, Q., Fang, Q., Liu, J., Chen, X., Liu, L., Zhan, X., Shan, H., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113064 · Cited by 56 · see citing works
Choueiri, T. K., Larkin, J., Pal, S. K., Motzer, R. J., Rini, B. I., Venugopal, B., Alekseev, B. Y., Miyake, H., Gravis, G., Bilen, M. A., et al. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100101 · Cited by 55 · see citing works
Stemness in solid malignancies: coping with immune attack
Agudo, J., & Miao, Y. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00760-0 · Cited by 54 · see citing works
Self-citationTargeting Myc-driven stress addiction in colorectal cancer
Saeed, H., Leibowitz, B. J., Zhang, L., & Yu, J. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.100963 · Cited by 53 · see citing works
Cell Death Pathway Regulation by Functional Nanomedicines for Robust Antitumor Immunity
Li, Y., Guo, Y., Zhang, K., Zhu, R., Chen, X. S., Zhang, Z., & Yang, W. (2023) · Advanced Science · doi:10.1002/advs.202306580 · Cited by 51 · see citing works
How Tumor Cell Dedifferentiation Drives Immune Evasion and Resistance to Immunotherapy
Li, J., & Stanger, B. Z. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1420 · Cited by 50 · see citing works
Han, Y., Xu, S., Ye, W., Wang, Y., Zhang, X., Deng, J., Zhang, Z., Liu, L., & Liu, S. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04297-0 · Cited by 49 · see citing works
Circular RNAs in tumor immunity and immunotherapy
Zhang, W., Chen, X., Yang, Z., Zhou, J., Peng, W., Zhang, X., Li, H., Qu, S., & Tao, K. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02082-z · Cited by 51 · see citing works
Ducarouge, B., Redavid, A. R., Victoor, C., Chira, R., Fonseca, A., Hervieu, M., Bergé, R., Lengrand, J., Vieugué, P., Neves, D., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01209-x · Cited by 46 · see citing works
Sadhukhan, P., Feng, M., Illingworth, E. J., Sloma, I., Ooki, A., Matoso, A., Sidransky, D., Johnson, B. A., Marchionni, L., Sillé, F. C. M., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci171164 · Cited by 47 · see citing works
An emerging role for cellular crosstalk in the cancer stem cell niche
Oshimori, N., Guo, Y., & Taniguchi, S. (2021) · The Journal of Pathology · doi:10.1002/path.5655 · Cited by 47 · see citing works
Immunotargeting of Cancer Stem Cells
Köseer, A. S., Gaetano, S. D., Arndt, C., Bachmann, M. P., & Dubrovska, A. (2023) · Cancers · doi:10.3390/cancers15051608 · Cited by 46 · see citing works
Chen, B., Mu, C., Zhang, Z., He, X., & Liu, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.891268 · Cited by 46 · see citing works
Kursunel, M. A., Taşkıran, E. Z., Tavukçuoğlu, E., Yanık, H., Demirağ, F., Karaosmanoğlu, B., Kurt, F. G. Ö., Üner, A., Esendagli, D. R., Kızılgöz, D., et al. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-02998-1 · Cited by 42 · see citing works
Ray, D., Yun, Y. C., Idris, M., Cheng, S., Boot, A., Iain, T. B. H., Rozen, S., Tan, P. B. O., & Epstein, D. M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002499117 · Cited by 42 · see citing works
Moutafi, M. K., Molero-Abraham, M., Martínez-Morilla, S., Baena, J., Vathiotis, I. A., Gavrielatou, N., Castro‐Labrador, L., Ponce, G. R. D. G., Adradas, V., Orive, D., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-004757 · Cited by 42 · see citing works
Xu, X., Yu, Y., Zhang, W., Ma, W., He, C., Qiu, G., Wang, X., Liu, Q., Zhao, M.-Y., Xie, J.-Y., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01349-3 · Cited by 38 · see citing works
Xuan, Y., Sheng, Y., Zhang, D., Zhang, K., Zhang, Z., Yü, P., Wang, S., Shi, X., Lian, J., Liu, K., et al. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101138 · Cited by 39 · see citing works
Sniping Cancer Stem Cells with Nanomaterials
Wang, W.-D., Guo, Y., Yang, Z., Su, G.-L., & Sun, Z. (2023) · ACS Nano · doi:10.1021/acsnano.3c07828 · Cited by 38 · see citing works
Minimal Residual Disease, Metastasis and Immunity
Badia-Ramentol, J., Linares, J., Gómez‐Llonín, A., & Calon, A. (2021) · Biomolecules · doi:10.3390/biom11020130 · Cited by 39 · see citing works
Epithelial-mesenchymal transition in cancer stemness and heterogeneity: updated
Mortezaee, K., Majidpoor, J., & Kharazinejad, E. (2022) · Medical Oncology · doi:10.1007/s12032-022-01801-0 · Cited by 38 · see citing works
- Authors
- Miao, Y., Yang, H., Levorse, J., Yuan, S., Polak, L., Sribour, M., Singh, B., Rosenblum, M. D., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Fuchs, Elaine
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 177
- Issue
- 5
- Pages
- 1172-1186.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6525024
- OpenAlex
- W2942376604
- Cited by
- 299
- References
- 52
- Citations by year
- 2026: 29 · 2025: 35 · 2024: 43 · 2023: 51 · 2022: 36 · 2021: 49 · 2020: 41 · 2019: 15
- FWCI
- 14.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institutes of Health (R01-AR050452, R- 01AR27883, C32585GG)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- adaptive immune resistance, squamous cell carcinoma, skin cancer, TGF-beta, CD80, CTLA-4, immune checkpoint, tumor recurrence, immune evasion, cancer stem cells
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Humans, Immunity, Cellular, Immunologic Surveillance, Mice, Transgenic, Neoplasm Proteins, Skin Neoplasms, T-Lymphocytes, Neoplastic Stem Cells, Adoptive Transfer, Cell Line, Tumor, Mice
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