5 results on '"Hensley, Scott E."'
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2. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer
- Author
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Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A. G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R., Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A., Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.
- Published
- 2021
- Full Text
- View/download PDF
3. CD8
- Author
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Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A.G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R, Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A, Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.
- Subjects
Male ,B-Lymphocytes ,Immunity, Cellular ,SARS-CoV-2 ,COVID-19 ,CD8-Positive T-Lymphocytes ,Middle Aged ,Antibodies, Viral ,Article ,Immunity, Humoral ,Immunophenotyping ,Cohort Studies ,Survival Rate ,Logistic Models ,Hematologic Neoplasms ,Neoplasms ,Multivariate Analysis ,Humans ,Female ,Prospective Studies ,Aged ,Proportional Hazards Models - Abstract
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.
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- 2021
4. Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses
- Author
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Lasaro, Marcio O., Tatsis, Nia, Hensley, Scott E., Whitbeck, J. Charles, Lin, Shih-Wen, Rux, John J., Wherry, E. John, Cohen, Gary H., Eisenberg, Roselyn J., and Ertl, Hildegund C.
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Herpesviruses -- Health aspects ,Herpesviruses -- Genetic aspects ,Herpesviruses -- Research ,Immune response -- Physiological aspects ,Immune response -- Research ,Protein binding -- Physiological aspects ,Protein binding -- Research ,T cells -- Health aspects ,T cells -- Genetic aspects ,T cells -- Research - Abstract
Interactions between the herpesvirus entry mediator (HVEM) and the B- and T-lymphocyte attenuator (BTLA) inhibit B and T cell activation. HVEM-BTLA interactions are blocked by herpes simplex virus (HSV) glycoprotein D (gD) through binding of its N-terminal domain to the BTLA binding site of HVEM. In this study, we inserted viral antigens into the C-terminal domain of gD and expressed these antigens with plasmid or E1-deleted (replication-defective) adenovirus vectors. Viral antigens fused to gD induced T and B cell responses to the antigen that were far more potent than those elicited by the same antigen expressed without gD. The immunopotentiating effect required binding of the gD chimeric protein to HVEM. Overall, the studies demonstrate that targeting of antigen to the BTLA binding site of HVEM augments the immunogenicity of vaccines., Interactions between HVEM, a member of the tumor necrosis factor receptor family, and LIGHT (a protein that is homologous to lymphotoxin, is inducible, competes for gD of herpesvirus, binds HVEM [...]
- Published
- 2008
5. CD8+T cells contribute to survival in patients with COVID-19 and hematologic cancer
- Author
-
Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A. G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R., Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A., Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.
- Abstract
Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.
- Published
- 2021
- Full Text
- View/download PDF
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