tetano
Editor, Senior Moderator
Viruses
. 2021 Nov 3;13(11):2212.
doi: 10.3390/v13112212.
Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
Juan Pablo Cerapio[SUP] 1 2 3 4 5 [/SUP], Marion Perrier[SUP] 1 2 3 4 5 [/SUP], Fréderic Pont[SUP] 1 2 3 4 5 [/SUP], Marie Tosolini[SUP] 1 2 3 4 5 [/SUP], Camille Laurent[SUP] 1 2 3 4 5 6 7 [/SUP], Stéphane Bertani[SUP] 2 8 [/SUP], Jean-Jacques Fournie[SUP] 1 2 3 4 5 6 [/SUP]
Affiliations
Abstract
The detailed characterization of human γδ 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 γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ 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-Barr virus-positive Hodgkin's lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ 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 γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ 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 γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.
Keywords: COVID-19; differentiation; gammadelta; human; lymphocyte; single cell; trajectory; transcriptome; tumor.
. 2021 Nov 3;13(11):2212.
doi: 10.3390/v13112212.
Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
Juan Pablo Cerapio[SUP] 1 2 3 4 5 [/SUP], Marion Perrier[SUP] 1 2 3 4 5 [/SUP], Fréderic Pont[SUP] 1 2 3 4 5 [/SUP], Marie Tosolini[SUP] 1 2 3 4 5 [/SUP], Camille Laurent[SUP] 1 2 3 4 5 6 7 [/SUP], Stéphane Bertani[SUP] 2 8 [/SUP], Jean-Jacques Fournie[SUP] 1 2 3 4 5 6 [/SUP]
Affiliations
- PMID: 34835019
- DOI: 10.3390/v13112212
Abstract
The detailed characterization of human γδ 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 γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ 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-Barr virus-positive Hodgkin's lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ 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 γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ 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 γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.
Keywords: COVID-19; differentiation; gammadelta; human; lymphocyte; single cell; trajectory; transcriptome; tumor.