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.
Subject(s)
COVID-19/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Neoplasms/immunology , RNA-Seq , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Adult , Bronchoalveolar Lavage Fluid/immunology , COVID-19/complications , Cell Differentiation , Child , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/virology , Herpesvirus 4, Human/isolation & purification , Hodgkin Disease/immunology , Hodgkin Disease/virology , Humans , Lung/immunology , Lymphocyte Activation , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/physiology , Neoplasms/virology , Papillomaviridae/isolation & purification , Severity of Illness Index , Single-Cell Analysis , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocyte Subsets/physiologySubject(s)
COVID-19/complications , COVID-19/diagnosis , Hodgkin Disease/complications , Hodgkin Disease/diagnosis , SARS-CoV-2 , COVID-19/immunology , COVID-19/therapy , Clinical Decision-Making , Disease Management , Hodgkin Disease/drug therapy , Hodgkin Disease/immunology , Humans , Male , Middle Aged , Patient Outcome AssessmentABSTRACT
The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.