CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Autor:	Bange EM; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Han NA; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania., Wileyto P; Abramson Cancer Center, University of Pennsylvania.; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania., Kim JY; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania., Gouma S; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania., Robinson J; Abramson Cancer Center, University of Pennsylvania., Greenplate AR; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania., Porterfield F; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Owoyemi O; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Naik K; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Zheng C; Abramson Cancer Center, University of Pennsylvania., Galantino M; Abramson Cancer Center, University of Pennsylvania., Weisman AR; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Ittner CAG; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Kugler EM; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Baxter AE; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania., Oniyide O; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Agyekum RS; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Dunn TG; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Jones TK; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Giannini HM; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Weirick ME; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania., McAllister CM; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania., Babady NE; Department of Medicine, Memorial Sloan Kettering Cancer Center.; Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center., Kumar A; Department of Medicine, Memorial Sloan Kettering Cancer Center., Widman AJ; Department of Medicine, Memorial Sloan Kettering Cancer Center., DeWolf S; Department of Medicine, Memorial Sloan Kettering Cancer Center., Boutemine SR; Department of Medicine, Memorial Sloan Kettering Cancer Center., Roberts C; Abramson Cancer Center, University of Pennsylvania., Budzik KR; Abramson Cancer Center, University of Pennsylvania., Tollett S; Abramson Cancer Center, University of Pennsylvania., Wright C; Abramson Cancer Center, University of Pennsylvania., Perloff T; Abramson Cancer Center, University of Pennsylvania.; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, Pennsylvania Hospital., Sun L; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Mathew D; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania., Giles JR; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy., Oldridge DA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania., Wu JE; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy., Alanio C; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy., Adamski S; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania., Garfall AL; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Vella L; Department of Pediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia., Kerr SJ; Abramson Cancer Center, University of Pennsylvania.; Division of Hematology/Oncology, Department of Medicine, Lancaster General Hospital., Cohen JV; Abramson Cancer Center, University of Pennsylvania.; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, Pennsylvania Hospital., Oyer RA; Abramson Cancer Center, University of Pennsylvania.; Division of Hematology/Oncology, Department of Medicine, Lancaster General Hospital., Massa R; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania.; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, Presbyterian Hospital., Maillard IP; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Maxwell KN; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Reilly JP; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., Maslak PG; Department of Medicine, Memorial Sloan Kettering Cancer Center.; Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center., Vonderheide RH; Abramson Cancer Center, University of Pennsylvania.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy., Wolchok JD; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.; Department of Medicine, Memorial Sloan Kettering Cancer Center., Hensley SE; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania., Wherry EJ; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy., Meyer N; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania., DeMichele AM; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Vardhana SA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.; Department of Medicine, Memorial Sloan Kettering Cancer Center.; Parker Institute for Cancer Immunotherapy., Mamtani R; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania., Huang AC; Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.; Abramson Cancer Center, University of Pennsylvania.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania.; Parker Institute for Cancer Immunotherapy.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2021 Feb 02. Date of Electronic Publication: 2021 Feb 02.
DOI:	10.21203/rs.3.rs-162289/v1
Abstrakt:	Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu