Publications by authors named "Daniel C Rose"

Previously designed flow cytometry panels have provided a framework to analyze T-cell activation; however, few provide an extensive view of lymphocyte populations, and none are optimized for murine models. This article describes a panel designed specifically to assess the expression of activation and exhaustion markers in expanding lymphocyte populations in tumor-bearing mice across two distinct genetic backgrounds: BALB/c and C57BL/6. This comprehensive panel enables the assessment of multiple functional states and immune checkpoint markers across cytotoxic CD8 T cells, helper and regulatory CD4 T cells and natural killer cells in murine whole blood, lymph nodes and tumor.

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Article Synopsis
  • The study investigates how combining bempegaldesleukin (BEMPEG), an immunostimulatory cytokine prodrug, with intratumoral therapy using NKTR-262, a TLR 7/8 agonist, enhances the immune response and survival in tumor-bearing mice.
  • Results showed that the BEMPEG+NKTR-262 combination improved survival rates compared to BEMPEG with radiation therapy (RT), relying on CD8 T cells, which are crucial for the immune response.
  • The combination therapy led to an increase in activation markers in CD8 T cells in the blood and correlated with reduced tumor size, highlighting its effectiveness in boosting tumor-specific immunity.
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Background: High-dose radiotherapy (RT) is known to be immunogenic, but is rarely capable of driving clinically relevant abscopal antitumor immunity as monotherapy. RT is known to increase antigen presentation, type I/II interferon responses, and immune cell trafficking to irradiated tumors. Bempegaldesleukin (NKTR-214) is a CD122-preferential interleukin 2 (IL-2) pathway agonist that has been shown to increase tumor-infiltrating lymphocytes, T cell clonality, and increase PD-1 expression.

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