Data from Arming Tumor-Associated Macrophages to Reverse Epithelial Cancer Progression

• DOI: 10.1158/0008-5472.c.6510915.v1
• Publication Date: 2023-03-31T04:48:18Z
• Authors: Hiromi I. Wettersten; Sara M. Weis; Paulina Pathria; Tami Von Schalscha; Toshiyuki Minami; Judith A. Varner; David A. Cheresh
• Keywords: Tumor progression

<div>Abstract<p>Tumor-associated macrophages (TAM) are highly expressed within the tumor microenvironment of a wide range cancers, where they exert protumor phenotype by promoting cell growth and suppressing antitumor immune function. Here, we show that TAM accumulation in human mouse tumors correlates with expression integrin αvβ3, known driver epithelial cancer progression drug resistance. A monoclonal antibody targeting αvβ3 (LM609) exploited coenrichment TAMs to not only eradicate aggressive drug-resistant lung pancreas cancers mice, but also prevent emergence circulating cells. Importantly, this activity mice was eliminated following macrophage depletion. Although LM609 had no direct effect on viability, it engaged natural killer (NK) cells induce antibody-dependent cellular cytotoxicity (ADCC) αvβ3-expressing despite their CD47 “don't eat me” signal. In contrast strategies designed eliminate TAMs, these findings suggest anti-αvβ3 represents promising immunotherapeutic approach redirect serve as killers for late-stage or cancers.</p>Significance:<p>Therapeutic antibodies commonly engineered optimize engagement NK effectors. contrast, targets suppress enhance sensitivity exploiting trigger ADCC.</p></div>