{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:26:56Z","timestamp":1790468816131,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"publisher","award":["Institutional grant U1037"],"award-info":[{"award-number":["Institutional grant U1037"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Labex Toulouse Cancer (TOUCAN)","award":["ANR11-LABX"],"award-info":[{"award-number":["ANR11-LABX"]}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["PGA1-RF2019-0208691"],"award-info":[{"award-number":["PGA1-RF2019-0208691"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The detailed characterization of human \u03b3\u03b4 T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of \u03b3\u03b4 T cells and a robust mapping method for additional \u03b3\u03b4 T lymphocytes. Here, we incepted such a method to characterize thousands of \u03b3\u03b4 T lymphocytes from (n = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein\u2013Barr virus-positive Hodgkin\u2019s lymphoma have \u03b3\u03b4 tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRV\u03b39 and TCRV\u03b3non9 subsets of \u03b3\u03b4 T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of \u03b3\u03b4 T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes \u03b3\u03b4 T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar \u03b3\u03b4 T cell lymphopenia to that seen in adult patients. However, blood \u03b3\u03b4 T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory \u03b3\u03b4 T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.<\/jats:p>","DOI":"10.3390\/v13112212","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T21:57:49Z","timestamp":1635976669000},"page":"2212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Single-Cell RNAseq Profiling of Human \u03b3\u03b4 T Lymphocytes in Virus-Related Cancers and COVID-19 Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Juan Pablo","family":"Cerapio","sequence":"first","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Perrier","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5493-527X","authenticated-orcid":false,"given":"Fr\u00e9deric","family":"Pont","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-5952","authenticated-orcid":false,"given":"Marie","family":"Tosolini","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Laurent","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"},{"name":"Institut Carnot Lymphome CALYM, 75014 Paris, France"},{"name":"Centre Hospitalier Universitaire, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0398-9745","authenticated-orcid":false,"given":"St\u00e9phane","family":"Bertani","sequence":"additional","affiliation":[{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"PHARMADEV, IRD UMR 152, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Fournie","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse, Inserm UMR 1037, 31037 Toulouse, France"},{"name":"Toulouse University, 31062 Toulouse, France"},{"name":"CNRS UMR 5071, 31024 Toulouse, France"},{"name":"Institut Universitaire du Cancer-Oncopole de Toulouse, 31100 Toulouse, France"},{"name":"Laboratoire d\u2019Excellence \u2018TOUCAN-2\u2019, 31037 Toulouse, France"},{"name":"Institut Carnot Lymphome CALYM, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-immunol-102819-023144","article-title":"The Innate Biologies of Adaptive Antigen Receptors","volume":"38","author":"Hayday","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1084\/jem.20030235","article-title":"Differentiation of Effector\/Memory V\u03b42 T Cells and Migratory Routes in Lymph Nodes or Inflammatory Sites","volume":"198","author":"Dieli","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.4049\/jimmunol.145.10.3202","article-title":"Human V Gamma 9-V Delta 2 T Cell Receptor-Gamma Delta Lymphocytes Show Specificity to Daudi Burkitt\u2019s Lymphoma Cells","volume":"145","author":"Sturm","year":"1990","journal-title":"J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5392","DOI":"10.4049\/jimmunol.152.11.5392","article-title":"Unique Antigen Recognition by a Herpesvirus-Specific Tcr-Gamma Delta Cell","volume":"152","author":"Sciammas","year":"1994","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/BF03401668","article-title":"Functional gamma delta T-lymphocyte defect associated with human immunodeficiency virus infections","volume":"3","author":"Wallace","year":"1997","journal-title":"Molecular Med. Eng."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2174\/1566524023361880","article-title":"Innate T-Cell Immunity in HIV Infections: The Role of Vg9Vd2 T Lymphocytes","volume":"2","author":"Poccia","year":"2002","journal-title":"Curr. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.1128\/jvi.71.9.6427-6432.1997","article-title":"Isolation and characterization of human papillomavirus type 6-specific T cells infiltrating genital warts","volume":"71","author":"Hong","year":"1997","journal-title":"J. Virol."},{"key":"ref_8","first-page":"215","article-title":"Hepatosplenic gamma delta T-cell lymphoma associated with hepatitis B virus infection","volume":"44","author":"Ozaki","year":"1998","journal-title":"J. Med Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1086\/605413","article-title":"Phosphoantigen-Expanded Human \u03b3\u03b4 T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses","volume":"200","author":"Qin","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1079","DOI":"10.1002\/cti2.1079","article-title":"Human \u03b3\u03b4 T-cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation","volume":"8","author":"Sant","year":"2019","journal-title":"Clin. Transl. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.4049\/jimmunol.1303343","article-title":"Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human \u03b3\u03b4 T Cells against Dendritic Cells Infected with Dengue Virus","volume":"194","author":"Tsai","year":"2015","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1086\/502975","article-title":"Anti\u2013Severe Acute Respiratory Syndrome Coronavirus Immune Responses: The Role Played by V\u03b39V\u03b42 T Cells","volume":"193","author":"Poccia","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1172\/JCI5409","article-title":"Implication of \u03b3\u03b4 T cells in the human immune response to cytomegalovirus","volume":"103","author":"Merville","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.4049\/jimmunol.2000187","article-title":"Mobilization of \u03b3\u03b4 T Cells and IL-10 Production at the Acute Phase of Hepatitis E Virus Infection in Cytomegalovirus Carriers","volume":"206","author":"Fontaine","year":"2021","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.4049\/jimmunol.180.5.3417","article-title":"\u03b3\u03b4+T Cells Involvement in Viral Immune Control of Chronic Human Herpesvirus 8 Infection","volume":"180","author":"Barcy","year":"2008","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/s41423-020-0473-0","article-title":"More bricks in the wall against SARS-CoV-2 infection: Involvement of \u03b39\u03b42 T cells","volume":"17","author":"Rijkers","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-19080-6","article-title":"Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19","volume":"11","author":"Carissimo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jouan, Y., Guillon, A., Gonzalez, L., Perez, Y., Boisseau, C., Ehrmann, S., Ferreira, M., Daix, T., Jeannet, R., and Fran\u00e7ois, B. (2020). Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients. J. Exp. Med., 217.","DOI":"10.1084\/jem.20200872"},{"key":"ref_19","first-page":"1","article-title":"Whole-Transcriptome RNA Sequencing Reveals Significant Differentially Expressed mRNAs, miRNAs, and lncRNAs and Related Regulating Biological Pathways in the Peripheral Blood of COVID-19 Patients","volume":"2021","author":"Li","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kalici\u0144ska, E., Szymczak, D., Zi\u0144czuk, A., Adamik, B., Smiechowicz, J., Skalec, T., Nowicka-Suszko, D., Biernat, M., Bogucka-Fedorczuk, A., and Rybka, J. (2021). Immunosuppression as a Hallmark of Critical COVID-19: Prospective Study. Cells, 10.","DOI":"10.3390\/cells10061293"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/art.38928","article-title":"Review: Cancer-Induced Autoimmunity in the Rheumatic Diseases","volume":"67","author":"Shah","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1347742","DOI":"10.1080\/2162402X.2017.1347742","article-title":"Distinctive features of tumor-infiltrating \u03b3\u03b4 T lymphocytes in human colorectal cancer","volume":"6","author":"Meraviglia","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"eaax9364","DOI":"10.1126\/scitranslmed.aax9364","article-title":"An innate-like V\u03b41 + \u03b3\u03b4 T cell compartment in the human breast is associated with remission in triple-negative breast cancer","volume":"11","author":"Wu","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125884","DOI":"10.1172\/jci.insight.125884","article-title":"NKp46-expressing human gut-resident intraepithelial V\u03b41 T cell subpopulation exhibits high antitumor activity against colorectal cancer","volume":"4","author":"Mikulak","year":"2019","journal-title":"JCI Insight"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"0192","DOI":"10.1126\/scitranslmed.abb0192","article-title":"Characterization of ascites- and tumor-infiltrating \u03b3\u03b4 T cells reveals distinct repertoires and a beneficial role in ovarian cancer","volume":"13","author":"Foord","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11906","DOI":"10.1073\/pnas.1818488116","article-title":"Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRV\u03b41 and TCRV\u03b42 \u03b3\u03b4 T lymphocytes","volume":"116","author":"Pizzolato","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1939518","DOI":"10.1080\/2162402X.2021.1939518","article-title":"Phased differentiation of \u03b3\u03b4 T and T CD8 tumor-infiltrating lymphocytes revealed by single-cell transcriptomics of human cancers","volume":"10","author":"Cerapio","year":"2021","journal-title":"OncoImmunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1158\/2159-8290.CD-19-0680","article-title":"Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma","volume":"10","author":"Aoki","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.immuni.2019.11.014","article-title":"Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer","volume":"52","author":"Cillo","year":"2020","journal-title":"Immuni"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_32","unstructured":"McInnes, L., and Healy, J. (2021, October 12). UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. Available online: https:\/\/arxiv.org\/abs\/1802.03426."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gkz601","article-title":"Single-Cell Signature Explorer for comprehensive visualization of single cell signatures across scRNA-seq datasets","volume":"47","author":"Pont","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"lqaa025","DOI":"10.1093\/nargab\/lqaa025","article-title":"Single-Cell Virtual Cytometer allows user-friendly and versatile analysis and visualization of multimodal single cell RNAseq datasets","volume":"2","author":"Pont","year":"2020","journal-title":"NAR Genom. Bioinform."},{"key":"ref_35","first-page":"454","article-title":"Induction and transcriptional regulation of the co-inhibitory gene module in T cells","volume":"558","author":"Chihara","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","article-title":"TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection","volume":"571","author":"Alfei","year":"2019","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1188246","DOI":"10.1080\/2162402X.2016.1188246","article-title":"Large-scale microarray profiling reveals four stages of immune escape in non-Hodgkin lymphomas","volume":"5","author":"Tosolini","year":"2016","journal-title":"OncoImmunology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1158\/2326-6066.CIR-19-0855","article-title":"Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies","volume":"8","author":"Scarlata","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1016\/j.celrep.2017.08.078","article-title":"Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites","volume":"20","author":"Kumar","year":"2017","journal-title":"Cell Rep."},{"key":"ref_41","first-page":"274","article-title":"Peripheral T cell expansion predicts tumour infiltration and clinical response","volume":"579","author":"Wu","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nmeth.4628","article-title":"Alignment of single-cell trajectories to compare cellular expression dynamics","volume":"15","author":"Alpert","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_44","first-page":"1","article-title":"Trajectory-based differential expression analysis for single-cell sequencing data","volume":"11","author":"Berge","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lo Presti, E., and Dieli, F. (2021). and Meraviglia, S. Lymphopenia in COVID-19: Gammadelta T Cells-Based Therapeutic Opportunities. Vaccines (Basel), 9.","DOI":"10.3390\/vaccines9060562"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666983","DOI":"10.3389\/fimmu.2021.666983","article-title":"How to Train Your Dragon: Harnessing Gamma Delta T Cells Antiviral Functions and Trained Immunity in a Pandemic Era","volume":"12","author":"Caron","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1080\/1040841X.2020.1822279","article-title":"Making a case for using \u03b3\u03b4 T cells against SARS-CoV-2","volume":"46","author":"Yazdanifar","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Orumaa, K., and Dunne, M.R. (2021). The role of unconventional T cells in COVID-19. Ir. J. Med Sci., 1\u201310.","DOI":"10.1007\/s11845-021-02653-9"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11603","DOI":"10.1111\/jcmm.15620","article-title":"The phenotypic changes of \u03b3\u03b4 T cells in COVID-19 patients","volume":"24","author":"Lei","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1007\/s10875-020-00806-6","article-title":"Flow Cytometry Identifies Risk Factors and Dynamic Changes in Patients with COVID-19","volume":"40","author":"Moratto","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/s41591-020-1054-6","article-title":"Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection","volume":"26","author":"Carter","year":"2020","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-17834-w","article-title":"Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm","volume":"11","author":"Guo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10970","DOI":"10.1073\/pnas.2005615117","article-title":"Effective treatment of severe COVID-19 patients with tocilizumab","volume":"117","author":"Xu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1080\/14712598.2019.1634050","article-title":"\u03b3\u03b4 cell-based immunotherapy for cancer","volume":"19","author":"Presti","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-018-0130-2","article-title":"Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates","volume":"557","author":"Simoni","year":"2018","journal-title":"Nature"},{"key":"ref_56","first-page":"119","article-title":"Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma","volume":"596","author":"Oliveira","year":"2021","journal-title":"Nat. Cell Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:25:23Z","timestamp":1760167523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,3]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["v13112212"],"URL":"https:\/\/doi.org\/10.3390\/v13112212","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,3]]}}}