Abstract Details

Title Direct Evidence That Increase in Tumor-Associated Macrophages (TAMs) after Antiangiogenic Therapy Is Associated with Poor Survival in Recurrent Glioblastoma (GBM) Patients

Topic Neuro-oncology

Presentation(s) S35 - (-)

Poster/Presentation
Number 001

Objective

Background Anti-angiogenic therapy is associated with increased radiographic responses in GBMs, but tumors invariably recur. TAMs are thought to affect progression through anti-angiogenic therapy in preclinical models.

Design/Methods TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital; clinical information gained through review of the patients' records.

Results Using flow cytometry, we observed an increase in CD11b+CD14+ cells in the AAT+ patients compared to AAT- patients. IHC analysis demonstrated a significant increase in CD68+ macrophages in the tumor bulk (p<0.01) and infiltrative areas (p<0.05) in AAT+ patients. We also observed a significant increase in CD11b+ myeloid cells in the tumor bulk (p<0.01). In addition, there was a significant increase in CD163+ cells in infiltrative tumor (p<0.05). Finally, an increased number of CD68+ cells in infiltrative tumor (p=0.05) and CD11b+ cells in bulk and infiltrative tumor (p<0.05) was significantly correlated with poor overall survival in patients who first received anti-angiogenic therapy at recurrence.

Conclusions In summary, recurrent GBMs showed a significant increase in CD68+ TAMs and CD11b+ cells in the tumor bulk after anti-angiogenic therapy. There was also an increase in CD68+and CD163+ TAMs in the infiltrative regions. A greater number of CD68+ cells and CD11b+ cells in infiltrative tumor and CD11b+ cells in tumor bulk was associated with significantly decreased overall survival in recurrent GBM patients. These data indicate that TAMs may participate in escape from anti-angiogenic therapy and may represent a future therapeutic target in recurrent GBM.

Authors/Disclosures
Christine Lu-Emerson, MD PRESENTER	Dr. Lu-Emerson has received personal compensation in the range of $500-$4,999 for serving as a Member with National Cancer Institute Brain Malignancy Steering Committee.
	No disclosure on file
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Paolo Ragonese	No disclosure on file
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Tracy T. Batchelor, MD, MPH (Brigham and Women's Hospital)	Dr. Batchelor has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Up To Date, Inc. An immediate family member of Dr. Batchelor has received publishing royalties from a publication relating to health care. Dr. Batchelor has received publishing royalties from a publication relating to health care.
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