T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours.

Animals Cell- and Tissue-Based Therapy Immunotherapy, Adoptive Mesothelin Mice Pancreatic Neoplasms / therapy Receptors, CXCR6 / metabolism Receptors, Chemokine / genetics T-Lymphocytes

Journal

Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896

Informations de publication

Date de publication:
11 2021
Historique:
received: 11 05 2020
accepted: 26 04 2021
pubmed: 5 6 2021
medline: 21 1 2022
entrez: 4 6 2021
Statut: ppublish

Résumé

The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.

Identifiants

DOI: 10.1038/s41551-021-00737-6 PMID: 34083764 PMC: PMC7611996
pubmed: 34083764
doi: 10.1038/s41551-021-00737-6
pii: 10.1038/s41551-021-00737-6
pmc: PMC7611996
mid: EMS123298
doi:

Substances chimiques

Cxcr6 protein, mouse 0
Receptors, CXCR6 0
Receptors, Chemokine 0
Mesothelin J27WDC343N

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1246-1260

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI123349
Pays : United States
Organisme : European Research Council
ID : 866411
Pays : International
Organisme : NCI NIH HHS
ID : R00 CA215604
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA240239
Pays : United States
Organisme : European Research Council
ID : 756017
Pays : International

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348, 62–68 (2015).
pubmed: 25838374 pmcid: 6295668 doi: 10.1126/science.aaa4967
Kobold, S. et al. Immunotherapy in tumors. Dtsch. Ärztebl. Int. 112, 809–815 (2015).
pubmed: 26667979 pmcid: 4709658
Sheridan, C. First approval in sight for Novartis’ CAR-T therapy after panel vote. Nat. Biotechnol. 35, 691–693 (2017).
pubmed: 28787408 doi: 10.1038/nbt0817-691
Ahmed, N. et al. Human epidermal growth factor receptor 2 (HER2)—specific chimeric antigen recpetor-modified T cells for the immunotherapy of HER2-positive sarcoma. J. Clin. Oncol. 33, 1688–1696 (2015).
pubmed: 25800760 pmcid: 4429176 doi: 10.1200/JCO.2014.58.0225
Adusumilli, P. S. et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci. Transl. Med. 6, 261ra151 (2014).
pubmed: 25378643 pmcid: 4373413 doi: 10.1126/scitranslmed.3010162
Brown, C. E. et al. Regression of glioblastoma after chimeric antigen receptor T cell therapy. N. Engl. J. Med. 375, 2561–2569 (2016).
pubmed: 28029927 pmcid: 5390684 doi: 10.1056/NEJMoa1610497
O’Rourke, D. M. et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med. 9, eaaa0984 (2017).
pubmed: 28724573 pmcid: 5762203 doi: 10.1126/scitranslmed.aaa0984
Tchou, J. et al. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol. Res. 5, 1152–1161 (2017).
pubmed: 29109077 pmcid: 5712264 doi: 10.1158/2326-6066.CIR-17-0189
Akbay, E. A. et al. Interleukin-17A promotes lung tumor progression through neutrophil attraction to tumor sites and mediating resistance to PD-1 blockade. J. Thorac. Oncol. 12, 1268–1279 (2017).
pubmed: 28483607 pmcid: 5532066 doi: 10.1016/j.jtho.2017.04.017
Bauer, C. A. et al. Dynamic T
pubmed: 24812664 pmcid: 4089459 doi: 10.1172/JCI66375
Linke, B. et al. CXCL16/CXCR6-mediated adhesion of human peripheral blood mononuclear cells to inflamed endothelium. Cytokine 122, 154081 (2019).
pubmed: 28647282 doi: 10.1016/j.cyto.2017.06.008
Polański, K. et al. BBKNN: fast batch alignment of single cell transcriptomes. Bioinformatics 36, 964–965 (2020).
pubmed: 31400197 doi: 10.1093/bioinformatics/btz625
Tokarew, N., Ogonek, J., Endres, S., von Bergwelt-Baildon, M. & Kobold, S.Teaching an old dog new tricks: next-generation CAR T cells. Br. J. Cancer 120, 26–37 (2019).
pubmed: 30413825 doi: 10.1038/s41416-018-0325-1
Grosser, R., Cherkassky, L., Chintala, N. & Adusumilli, P. S. Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors. Cancer Cell 36, 471–482 (2019).
pubmed: 31715131 pmcid: 7171534 doi: 10.1016/j.ccell.2019.09.006
Rapp, M. et al. C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer. OncoImmunology 5, e1105428 (2016).
pubmed: 27195186 doi: 10.1080/2162402X.2015.1105428
Hughes, C. E. & Nibbs, R. J. B. A guide to chemokines and their receptors. FEBS J. 285, 2944–2971 (2018).
pubmed: 29637711 pmcid: 6120486 doi: 10.1111/febs.14466
Curiel, T. J. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942–949 (2004).
pubmed: 15322536 doi: 10.1038/nm1093
Lim, W. A. & June, C. H. The principles of engineering immune cells to treat cancer. Cell 168, 724–740 (2017).
pubmed: 28187291 pmcid: 5553442 doi: 10.1016/j.cell.2017.01.016
Garetto, S. et al. Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model. Oncotarget 7, 43010–43026 (2016).
pubmed: 27177227 pmcid: 5190004 doi: 10.18632/oncotarget.9280
Siddiqui, I., Erreni, M., van Brakel, M., Debets, R. & Allavena, P. Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient. J. Immunother. Cancer 4, 21 (2016).
pubmed: 27096098 pmcid: 4836203 doi: 10.1186/s40425-016-0125-1
Muller, N. et al. Engineering NK cells modified with an EGFRvIII-specific chimeric antigen receptor to overexpress CXCR4 improves immunotherapy of CXCL12/SDF-1α-secreting glioblastoma. J. Immunother. 38, 197–210 (2015).
pubmed: 25962108 pmcid: 4428685 doi: 10.1097/CJI.0000000000000082
Moon, E. K. et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin. Cancer Res. 17, 4719–4730 (2011).
pubmed: 21610146 pmcid: 3612507 doi: 10.1158/1078-0432.CCR-11-0351
Peng, W. et al. Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clin. Cancer Res. 16, 5458–5468 (2010).
pubmed: 20889916 pmcid: 3476703 doi: 10.1158/1078-0432.CCR-10-0712
Shimaoka, T. et al. Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J. Leukoc. Biol. 75, 267–274 (2004).
pubmed: 14634054 doi: 10.1189/jlb.1003465
Kobold, S. et al. Impact of a new fusion receptor on PD-1-mediated immunosuppression in adoptive T cell therapy. J. Natl Cancer Inst. 107, djv146 (2015).
pubmed: 26105028 pmcid: 4609553 doi: 10.1093/jnci/djv146
Li, K. et al. Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer. Int. J. Clin. Exp. Pathol. 8, 14725–14732 (2015).
pubmed: 26823797 pmcid: 4713583
Madissoon, E. et al. scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation. Genome Biol. 21, 1 (2019).
pubmed: 31892341 pmcid: 6937944 doi: 10.1186/s13059-019-1906-x
Deng, L., Chen, N., Li, Y., Zheng, H. & Lei, Q. CXCR6/CXCL16 functions as a regulator in metastasis and progression of cancer. Biochim. Biophys. Acta 1806, 42–49 (2010).
pubmed: 20122997
Wente, M. N. et al. Expression and potential function of the CXC chemokine CXCL16 in pancreatic ductal adenocarcinoma. Int. J. Oncol. 33, 297–308 (2008).
pubmed: 18636150
Heydtmann, M. et al. CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J. Immunol. 174, 1055–1062 (2005).
pubmed: 15634930 doi: 10.4049/jimmunol.174.2.1055
Rataj, F. et al. PD1–CD28 fusion protein enables CD4
Sato, T. et al. Role for CXCR6 in recruitment of activated CD8
pubmed: 15611250 doi: 10.4049/jimmunol.174.1.277
Unutmaz, D. et al. The primate lentiviral receptor Bonzo/STRL33 is coordinately regulated with CCR5 and its expression pattern is conserved between human and mouse. J. Immunol. 165, 3284–3292 (2000).
pubmed: 10975845 doi: 10.4049/jimmunol.165.6.3284
Karches, C. H. et al. Bispecific antibodies enable synthetic agonistic receptor-transduced T cells for tumor immunotherapy. Clin. Cancer Res. 25, 5890–5900 (2019).
pubmed: 31285373 pmcid: 7611266 doi: 10.1158/1078-0432.CCR-18-3927
Paulos, C. M. et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8
pubmed: 17657310 pmcid: 1924500 doi: 10.1172/JCI32205
Kobold, S. et al. Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer. J. Natl Cancer Inst. 107, 364 (2015).
pubmed: 25424197 doi: 10.1093/jnci/dju364
Chinnasamy, D. et al. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin. Cancer Res. 18, 1672–1683 (2012).
pubmed: 22291136 pmcid: 6390958 doi: 10.1158/1078-0432.CCR-11-3050
Jin, L. et al. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat. Commun. 10, 4016 (2019).
pubmed: 31488817 pmcid: 6728370 doi: 10.1038/s41467-019-11869-4
Bailey, P. et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531, 47–52 (2016).
pubmed: 26909576 doi: 10.1038/nature16965
Schizas, D. et al. Immunotherapy for pancreatic cancer: a 2020 update. Cancer Treat. Rev. 86, 102016 (2020).
pubmed: 32247999 doi: 10.1016/j.ctrv.2020.102016
Hartmann, N. et al. Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer. Clin. Cancer Res. 20, 3422–3433 (2014).
pubmed: 24763614 doi: 10.1158/1078-0432.CCR-13-2972
Kocher, H. M. et al. Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer. Nat. Commun. 11, 4841 (2020).
pubmed: 32973176 pmcid: 7518421 doi: 10.1038/s41467-020-18636-w
Alvarez, R. et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br. J. Cancer 109, 926–933 (2013).
pubmed: 23907428 pmcid: 3749580 doi: 10.1038/bjc.2013.415
Lo, A. et al. Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res. 75, 2800–2810 (2015).
pubmed: 25979873 pmcid: 4506263 doi: 10.1158/0008-5472.CAN-14-3041
Matloubian, M., David, A., Engel, S., Ryan, J. E. & Cyster, J. G. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat. Immunol. 1, 298–304 (2000).
pubmed: 11017100 doi: 10.1038/79738
Linke, B. et al. CXCL16/CXCR6-mediated adhesion of human peripheral blood mononuclear cells to inflamed endothelium. Cytokine 122, 154081 (2019).
pubmed: 28647282 doi: 10.1016/j.cyto.2017.06.008
Collado, A. et al. Functional role of endothelial CXCL16/CXCR6–platelet–leucocyte axis in angiotensin II-associated metabolic disorders. Cardiovasc. Res. 114, 1764–1775 (2018).
pubmed: 29800106 doi: 10.1093/cvr/cvy135
Sackstein, R., Schatton, T. & Barthel, S. R. T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy. Lab. Invest. 97, 669–697 (2017).
pubmed: 28346400 pmcid: 5446300 doi: 10.1038/labinvest.2017.25
Agostini, C. et al. Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis. Am. J. Respir. Crit. Care Med. 172, 1290–1298 (2005).
pubmed: 16100013 doi: 10.1164/rccm.200501-142OC
Oldham, K. A. et al. T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6. Eur. Urol. 61, 385–394 (2012).
pubmed: 22079021 doi: 10.1016/j.eururo.2011.10.035
La Porta, C. A. CXCR6: the role of environment in tumor progression. Challenges for therapy. Stem Cell Rev. 8, 1282–1285 (2012).
doi: 10.1007/s12015-012-9383-6
Allaoui, R. et al. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Nat. Commun. 7, 13050 (2016).
pubmed: 27725631 pmcid: 5062608 doi: 10.1038/ncomms13050
Chalabi-Dchar, M. et al. Loss of somatostatin receptor subtype 2 promotes growth of KRAS-induced pancreatic tumors in mice by activating PI3K signaling and overexpression of CXCL16. Gastroenterology 148, 1452–1465 (2015).
pubmed: 25683115 doi: 10.1053/j.gastro.2015.02.009
Elyada, E. et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 9, 1102–1123 (2019).
pubmed: 31197017 pmcid: 6727976 doi: 10.1158/2159-8290.CD-19-0094
Hu, W., Liu, Y., Zhou, W., Si, L. & Ren, L. CXCL16 and CXCR6 are coexpressed in human lung cancer in vivo and mediate the invasion of lung cancer cell lines in vitro. PLoS ONE 9, e99056 (2014).
pubmed: 24897301 pmcid: 4045941 doi: 10.1371/journal.pone.0099056
Slaga, D. et al. Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3. Sci. Transl. Med. 10, eaat5775 (2018).
pubmed: 30333240 doi: 10.1126/scitranslmed.aat5775
Morello, A., Sadelain, M. & Adusumilli, P. S. Mesothelin-targeted CARs: driving T cells to solid tumors. Cancer Discov 6, 133–146 (2016).
pubmed: 26503962 doi: 10.1158/2159-8290.CD-15-0583
Beatty, G. L. et al. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology 155, 29–32 (2018).
pubmed: 29567081 doi: 10.1053/j.gastro.2018.03.029
Fujita, K. et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin. Cancer Res. 1, 501–507 (1995).
pubmed: 9816009
Hall, M. et al. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. J. Immunother. Cancer 4, 61 (2016).
pubmed: 27777771 pmcid: 5067894 doi: 10.1186/s40425-016-0164-7
Nanki, T. et al. Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis. Arthritis Rheum. 52, 3004–3014 (2005).
pubmed: 16200580 doi: 10.1002/art.21301
Akce, M., Zaidi, M. Y., Waller, E. K., El-Rayes, B. F. & Lesinski, G. B. The potential of CAR T cell therapy in pancreatic cancer. Front. Immunol. 9, 2166 (2018).
pubmed: 30319627 pmcid: 6167429 doi: 10.3389/fimmu.2018.02166
Jacobs, C. et al. An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma. Int. J. Cancer 128, 897–907 (2011).
pubmed: 20473889 doi: 10.1002/ijc.25399
Anz, D. et al. Suppression of intratumoral CCL22 by type I interferon inhibits migration of regulatory T cells and blocks cancer progression. Cancer Res. 75, 4483–4493 (2015).
pubmed: 26432403 doi: 10.1158/0008-5472.CAN-14-3499
Ghani, K. et al. Efficient human hematopoietic cell transduction using RD114- and GALV-pseudotyped retroviral vectors produced in suspension and serum-free media. Hum. Gene Ther. 20, 966–974 (2009).
pubmed: 19453219 pmcid: 2861952 doi: 10.1089/hum.2009.001
Metzger, P. et al. Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer. J. Immunother. Cancer 7, 288 (2019).
pubmed: 31694706 pmcid: 6836385 doi: 10.1186/s40425-019-0778-7
Larimer, B. M. et al. Granzyme B PET imaging as a predictive biomarker of immunotherapy response. Cancer Res. 77, 2318–2327 (2017).
pubmed: 28461564 pmcid: 5474226 doi: 10.1158/0008-5472.CAN-16-3346
Larimer, B. M. et al. The effectiveness of checkpoint inhibitor combinations and administration timing can be measured by granzyme B pet imaging. Clin. Cancer Res. 25, 1196–1205 (2019).
pubmed: 30327313 doi: 10.1158/1078-0432.CCR-18-2407
Rühland, S. et al. Quantification of in vitro mesenchymal stem cell invasion into tumor spheroids using selective plane illumination microscopy. J. Biomed. Opt. 20, 040501 (2015).
pubmed: 25839427 doi: 10.1117/1.JBO.20.4.040501
Schmohl, K. A. et al. Thyroid hormones and tetrac: new regulators of tumour stroma formation via integrin αvβ3. Endocr. Relat. Cancer 22, 941–952 (2015).
pubmed: 26307023 doi: 10.1530/ERC-15-0245
Renz, B. W. et al. β2 adrenergic–neurotrophin feedforward loop promotes pancreatic cancer. Cancer Cell. 33, 75–90.e7 (2018).
pubmed: 29249692 doi: 10.1016/j.ccell.2017.11.007
Renz, B. W. et al. Cholinergic signaling via muscarinic receptors directly and indirectly suppresses pancreatic tumorigenesis and cancer stemness. Cancer Discov. 8, 1458–1473 (2018).
pubmed: 30185628 pmcid: 6214763 doi: 10.1158/2159-8290.CD-18-0046
Ruess, D. A. et al. Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase. Nat. Med. 24, 954–960 (2018).
pubmed: 29808009 doi: 10.1038/s41591-018-0024-8
Reichert, M. et al. Isolation, culture and genetic manipulation of mouse pancreatic ductal cells. Nat. Protoc. 8, 1354–1365 (2013).
pubmed: 23787893 pmcid: 4121532 doi: 10.1038/nprot.2013.079
Halama, N. et al. Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell 29, 587–601 (2016).
pubmed: 27070705 doi: 10.1016/j.ccell.2016.03.005
Halama, N. et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 71, 5670–5677 (2011).
pubmed: 21846824 doi: 10.1158/0008-5472.CAN-11-0268
Goldman, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat. Biotechnol. 38, 675–678 (2020).
pubmed: 32444850 pmcid: 7386072 doi: 10.1038/s41587-020-0546-8
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15–15 (2018).
pubmed: 29409532 pmcid: 5802054 doi: 10.1186/s13059-017-1382-0
Travaglini, K. J. et al. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature 587, 619–625 (2020).
pubmed: 33208946 pmcid: 7704697 doi: 10.1038/s41586-020-2922-4
Reyfman, P. A. et al. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 199, 1517–1536 (2019).
pubmed: 30554520 pmcid: 6580683 doi: 10.1164/rccm.201712-2410OC
Peng, J. et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 29, 725–738 (2019).
pubmed: 31273297 pmcid: 6796938 doi: 10.1038/s41422-019-0195-y
Baron, M. et al. A single-cell transcriptomic map of the human and mouse pancreas reveals inter- and intra-cell population structure. Cell Syst. 3, 346–360 (2016).
pubmed: 27667365 pmcid: 5228327 doi: 10.1016/j.cels.2016.08.011
Lun, A. T. L., Bach, K. & Marioni, J. C. Pooling across cells to normalize single-cell RNA sequencing data with many zero counts. Genome Biol. 17, 75 (2016).
pubmed: 27122128 doi: 10.1186/s13059-016-0947-7
Zheng, G. X. Y. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
pubmed: 28091601 pmcid: 5241818 doi: 10.1038/ncomms14049
McInnes L., Healy J. & Melville J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https://arxiv.org/abs/1802.03426 (2020).
Muus, C. et al. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat. Med. 27, 546–559 (2021).
pubmed: 33654293 doi: 10.1038/s41591-020-01227-z

Auteurs

Stefanie Lesch (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0003-2658-7666

Viktoria Blumenberg (V)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0003-1379-0876

Stefan Stoiber (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Adrian Gottschlich (A)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0002-2898-4182

Justyna Ogonek (J)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Bruno L Cadilha (BL)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0001-7045-3898

Zahra Dantes (Z)

Klinik und Poliklinik für Innere Medizin II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.

Felicitas Rataj (F)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Klara Dorman (K)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Johannes Lutz (J)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Clara H Karches (CH)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Constanze Heise (C)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Mathias Kurzay (M)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Benjamin M Larimer (BM)

Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0002-1288-7206

Simon Grassmann (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Moritz Rapp (M)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Alessia Nottebrock (A)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Stephan Kruger (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Nicholas Tokarew (N)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Philipp Metzger (P)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0001-8741-3139

Christine Hoerth (C)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Mohamed-Reda Benmebarek (MR)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0002-1201-7067

Dario Dhoqina (D)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Ruth Grünmeier (R)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Matthias Seifert (M)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0002-6581-6196

Arman Oener (A)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Öykü Umut (Ö)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Sandy Joaquina (S)

Université de Paris, Institute Cochin, INSERM, CNRS, Paris, France.
Equipe labellisée Ligue Contre le Cancer, Toulouse, France.

Lene Vimeux (L)

Université de Paris, Institute Cochin, INSERM, CNRS, Paris, France.
Equipe labellisée Ligue Contre le Cancer, Toulouse, France.

Thi Tran (T)

Equipe labellisée Ligue Contre le Cancer, Toulouse, France.
Université de Paris, PARCC, INSERM U970, Paris, France.

Thomas Hank (T)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-8087-2295

Taisuke Baba (T)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Duc Huynh (D)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Remco T A Megens (RTA)

Institute for Cardiovascular Prevention (IPEK), University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Cardiovascular Research Institute Maastricht (CARIM), Department of BioMedical Engineering, Maastricht University, Maastricht, the Netherlands.
ORCID: 0000-0001-9871-6696

Klaus-Peter Janssen (KP)

Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
ORCID: 0000-0002-4707-7887

Martin Jastroch (M)

Helmholtz Diabetes Center and German Diabetes Center (DZD), Helmholtz Zentrum München, Neuherberg, Germany.

Daniel Lamp (D)

Helmholtz Diabetes Center and German Diabetes Center (DZD), Helmholtz Zentrum München, Neuherberg, Germany.

Svenja Ruehland (S)

LMU Biocenter, Department Biology II, Ludwig Maximilians-Universität München, Munich, Germany.

Mauro Di Pilato (M)

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.

Jasper N Pruessmann (JN)

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.

Moritz Thomas (M)

Institute of Computational Biology, Helmholtz Zentrum München (German Research Center for Environmental Health), Neuherberg, Germany.
School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.

Carsten Marr (C)

Institute of Computational Biology, Helmholtz Zentrum München (German Research Center for Environmental Health), Neuherberg, Germany.

Steffen Ormanns (S)

Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.

Anna Reischer (A)

Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Michael Hristov (M)

Institute for Cardiovascular Prevention (IPEK), University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Eric Tartour (E)

Equipe labellisée Ligue Contre le Cancer, Toulouse, France.
Université de Paris, PARCC, INSERM U970, Paris, France.
Service d'Immunologie Biologique, APHP, Hôpital Européen Georges Pompidou, Paris, France.
ORCID: 0000-0002-7323-468X

Emmanuel Donnadieu (E)

Université de Paris, Institute Cochin, INSERM, CNRS, Paris, France.
Equipe labellisée Ligue Contre le Cancer, Toulouse, France.

Simon Rothenfusser (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany.
ORCID: 0000-0003-1151-7614

Peter Duewell (P)

Institute of Innate Immunity, University of Bonn, Bonn, Germany.

Lars M König (LM)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0002-8348-7787

Max Schnurr (M)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Marion Subklewe (M)

Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Andrew S Liss (AS)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-4040-9172

Niels Halama (N)

Department of Translational Immunotherapy, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0003-0344-6027

Maximilian Reichert (M)

Klinik und Poliklinik für Innere Medizin II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Center for Functional Protein Assemblies (CPA), Technische Universität München, Garching, Germany.
German Center for Translational Cancer Research (DKTK), Munich, Germany.

Thorsten R Mempel (TR)

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.

Stefan Endres (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany.
German Center for Translational Cancer Research (DKTK), Munich, Germany.
ORCID: 0000-0002-4703-537X

Sebastian Kobold (S)

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany. Sebastian.kobold@med.uni-muenchen.de.
Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany. Sebastian.kobold@med.uni-muenchen.de.
German Center for Translational Cancer Research (DKTK), Munich, Germany. Sebastian.kobold@med.uni-muenchen.de.
ORCID: 0000-0002-5612-4673

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Thérapeutique › Biothérapie › Thérapie cellulaire et tissulaire › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunisation passive › Transfert adoptif › Immunothérapie adoptive › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Mésothéline › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs viraux › Récepteurs CXCR6 › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux chimiokines › T cells armed with C-X-C chemokine receptor...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › T cells armed with C-X-C chemokine receptor...