GSE208122
MACROPHAGE CD5L IS A NOVEL TARGET FOR CANCER IMMUNOTHERAPY
Tumor associated macrophages (TAMs) can acquire an immunosuppressive, M2 polarization phenotype, thereby promoting tumor growth and protecting it from chemo or immuno-therapy. Since TAMs are plastic cells, their selective reprogramming presents an attractive therapeutic strategy. CD5L is a macrophage glycoprotein that controls key mechanisms in inflammatory responses and promotes M2 polarization. Here we report that CD5L TAMs expression in lung adenocarcinoma correlates with poor outcome. Additionally, cancer cell CMs induced macrophage M2 polarization and enhanced CD5L expression. We have raised a novel monoclonal antibody (mAb), RImAb, that specifically binds to human and mouse CD5L and blocks its M2 polarizing activity. RImAb administration reduced tumor growth in a mouse subcutaneous syngeneic model of lung cancer and modified the tumor microenvironment, altering intratumoral immune cell population profile, decreasing vascularity, and increasing the inflammatory milieu. The present study reveals a key function for CD5L protein in modulating macrophage activity and its interactions within the TME. Targeting CD5L with a mAb, was able to reduce tumor growth and modulate the TME, thus representing a promising approach to cancer immunotherapy. Overall design: RNA-seq from CD45+CD11b+Ly6GlowLy6C+ cells were processed in control samples (n=3) and treated with RImAb (n=4).