SIGLEC-3 (CD33) serves as an effective target in tumor progression

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B961
Abstract ID: 6292

Presenting Author:
Yi-Jyun Lin , Research assistant at Academia Sinica

Abstract:

Human CD33 (Siglec-3) possesses an immune-receptor tyrosine-based inhibition motif (ITIM), which recruits Src homology 2 (SH2) containing phosphatases (SHP-1/2) and inositol phosphatase (SHIP) and exerts inhibitory effects. The structure and downstream signaling of CD33 bear similarity to programmed cell death protein-1 (PD-1), a promising target in cancer immune therapy. Previous studies indicate that CD33 serves as a therapeutic target in acute myeloid leukemia (AML), additionally, CD33 also acts as a prevalent surface marker of human myeloid-derived suppressor cells (MDSCs). According to the inhibitory signaling upon CD33        activation, CD33 may participate in tumor progression and the regulatory role of CD33 in solid tumors is still unclear. To investigate whether CD33 influences cancer progression, we established a melanoma tumor (B16F10) mouse model in monocyte/macrophage-specific human CD33 transgenic mice (hCD33 Tg mice, Cx3cr1^cre/-hCD33M^+/-). Compared to wild-type mice (WT), tumor growth and mortality were larger and higher in CD33 Tg mice. Moreover, an antagonistic anti-hCD33 monoclonal antibody (clone 4L3-46) treatment successfully attenuated tumor growth in hCD33 Tg mice and led to a restructuring of the infiltrating MDSCs population. These results indicate that human CD33 contributes to the advancement of tumors, and the blockade of CD33 represents a promising strategy in tumor therapy.