Charles Tannenbaum, PhD
Staff Scientist
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
One mechanism by which inflammation mediates tumor progression is via the recruitment of myeloid derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells that infiltrates tumors and promotes tumor progression by their production of both immunosuppressive and angiogenic molecules. Our recently published work indicates that the relative inflammatory nature of a tumor significantly affects the number, phenotype and functional activity of infiltrating myeloid cells, which in turn may govern whether it is mostly an MDSC-mediated angiogenic or immunosuppressive mechanism that is responsible for enhancing that tumor’s progression. Observations made using our murine tumor models (CT26, RENCA) engineered or not to express IL-1β now indicate that an inflammatory tumor microenvironment promotes the marked infiltration of largely neutrophilic, CD11b+Gr1+ hi cells, and that when assessed by RT/PCR, they are significantly more angiogenic than neutrophilic MDSCs within non-inflammatory tumors, or than monocytic MDSCs within the same inflammatory tumors. Current studies are focused on elucidating which tumor- and stromal-derived molecules downstream of IL-1β stimulation, if inhibited, would abrogate the production and/or elicitation of neutrophilic MDSCs, thereby slowing tumor progression. One candidate is BV8 (also known as prokineticin 2), a hematopoietic and purportedly chemotactic molecule uniquely synthesized by neutrophilic MDSCs that might also be responsible for the anti-VEGF resistance characterizing some tumors.
Biography
Education & Professional Highlights
Graduate School - Temple University
Philadelphia, PA USA
1987
Graduate School - Temple University
Philadelphia, PA USA
1983
Undergraduate - SUNY Binghamton
Binghamton, NY USA
1980
Research
Overall areas of interest
- Tumor immunology; tumor-induced immune suppression; chemokines; IL-12; Myeloid Derived Suppressor Cells; inflammation; Medical student education; Graduate student education
- Tools and expertise of lab
- IL-1β and its downstream effectors as mediators of tumor progression
- Define cell-cell interactions in tumor microenvironment
- Identify specific cytokine and chemokine synthesis distinguishing inflammatory from non-inflammatory tumors
- BV8 as a mediator of resistance to anti-angiogenic therapy of tumors
Collaborators
- Marcela Diaz-Montero
- Tom Hamilton
Lab Discoveries
- Defined role of Mig and IP-10 as mediators of IL-12 anti-tumor activity (Tannenbaum et al, Jl of Imm, 1998)
- TNF-induced ganglioside expression by RCC promotes T cell dysfunction (Das et al, Can Res, 2008; Raval et al, 2007)
- Bcl-2 protects T cells from RCC-induced apoptosis (Molto et al, Clin Can Res, 2003)
- MDSC Accumulation associated with expression of IL-1β, IL-8, CXCL5 and Mip- 1α (Naijar et al, Clin Can Res, 2017)
- Granulocytic MDSCs from inflammatory tumors are more angiogenic and immunosuppressive than monocytic MDSCs (Tannenbaum et al, Can Imm Res, 2019)
How could these discoveries help patients?
- Understanding downstream effectors of IL-12-mediated anti-tumor activity
- Novel therapies for controlling tumor angiogenesis
- Novel therapies for inhibiting inflammatory vs non-inflammatory tumors
Our Team
Selected Publications
View publications for Charles Tannenbaum, PhD
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