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Rewiring the myeloid cell response to adjuvants to improve tumor control

Description: Macrophage suppression of T cell responses in the tumor immune environment represents an important problem limiting cure of residual disease following radiation therapy. We use high quality preclinical models of radiation therapy and immunotherapy to understand the mechanisms of success and failure in myeloid suppression of the T cell control of tumors. This is combined with analysis of clinical samples to explore how a novel mechanistic interaction between immune cells determines immune mediated tumor control.

Funder: National Cancer Institute

Funding type: research

Funder scheme: R01

Start date: 2019-12-02

End date: 2024-11-30

Investigator: MICHAEL JAMES GOUGH

Institution: PROVIDENCE PORTLAND MEDICAL CENTER

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Funded outputs count: 26

Funder award ID: R01CA244142

OpenAlex ID: G6597581385

Fluorescence tracking CD8 T cells from tumor-draining lymph nodes to irradiated tumors and their activation in the tumor environment

2026 · David Friedman, Gwen Kramer, et al. · The Journal of Immunology · 1

Fluorescence tracking Treg movement identifies anti-CCR8 and radiation as a therapeutic combination

2025 · David J. Friedman, Sina Ramin, et al. · iScience · 1

The effect of macrophage inhibitors on the inflammatory response in a mouse model of heart failure 3242

2025 · Eugene Mensah Agyare, Stephen A. O’Barr, et al. · The Journal of Immunology

A novel small molecule Enpp1 inhibitor improves tumor control following radiation therapy by targeting stromal Enpp1 expression

2024 · Jason R Baird, Alejandro F Alice, et al. · Scientific Reports · 12

Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor

2024 · Gwen Kramer, Tiffany Blair, et al. · Scientific Reports · 16

The immunogenic radiation and new players in immunotherapy and targeted therapy for head and neck cancer

2023 · Shay Sharon, Narmeen Daher-Ghanem, et al. · Frontiers in Oral Health · 14

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer

2023 · Terry R. Medler, Tiffany C. Blair, et al. · Scientific Reports · 17

Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help

2023 · Terry R. Medler, Gwen Kramer, et al. · Scientific Reports · 19

Ex vivo analysis of radiation effects on tumor infiltrating immune cells using tumor explants

2022 · Aanchal Preet Kaur, Gwen Kramer, et al. · Methods in cell biology · 1

ICOS is upregulated on T cells following radiation and agonism combined with radiation results in enhanced tumor control

2022 · Tiffany Blair, Jason Baird, et al. · Scientific Reports · 17

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

2022 · Thomas Duhen, Michael J. Gough, et al. · Frontiers in Oral Health · 6

The paradox of radiation and T cells in tumors

2022 · Michael J. Gough, Marka R. Crittenden · Neoplasia · 48

Fluorescent tracking identifies key migratory dendritic cells in the lymph node after radiotherapy

2022 · Tiffany C Blair, Shelly Bambina, et al. · Life Science Alliance · 29

Listeria monocytogenes-infected human monocytic derived dendritic cells activate Vγ9Vδ2 T cells independently of HMBPP production

2021 · Alejandro F. Alice, Gwen Kramer, et al. · Scientific Reports · 10

Explant Modeling of the Immune Environment of Head and Neck Cancer

2021 · Shay Sharon, Thomas Duhen, et al. · Frontiers in Oncology · 12

A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection

2021 · Shay Sharon, Jason R. Baird, et al. · Oncotarget · 5

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma

2021 · Rom Leidner, Marka Crittenden, et al. · Journal for ImmunoTherapy of Cancer · 194

The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors

2021 · Tiffany C. Blair, Alejandro F. Alice, et al. · Frontiers in Oncology · 18

Defining Immunogenic and Radioimmunogenic Tumors

2021 · Terry R. Medler, Tiffany C. Blair, et al. · Frontiers in Oncology · 36

Transcriptional and immunohistological assessment of immune infiltration in pancreatic cancer

2020 · Brady Bernard, Venkatesh Rajamanickam, et al. · PLoS ONE · 13

Transcriptional Upregulation of NLRC5 by Radiation Drives STING- and Interferon-Independent MHC-I Expression on Cancer Cells and T Cell Cytotoxicity

2020 · Lauren K. Zebertavage, Alejandro Alice, et al. · Scientific Reports · 76

Dendritic Cell Maturation Defines Immunological Responsiveness of Tumors to Radiation Therapy

2020 · Tiffany C Blair, Shelly Bambina, et al. · The Journal of Immunology · 66

Targeting MerTK Enhances Adaptive Immune Responses After Radiation Therapy

2020 · Garth W. Tormoen, Tiffany C. Blair, et al. · International Journal of Radiation Oncology*Biology*Physics · 29

Using Preclinical Data to Design Combination Clinical Trials of Radiation Therapy and Immunotherapy

2020 · Michael J. Gough, Shay Sharon, et al. · Seminars in Radiation Oncology · 15

A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity

2019 · Lauren Zebertavage, Shelly Bambina, et al. · PLoS ONE · 24