Blocking Clever-1 on human monocytes inhibits the growth of aggressive breast cancer
Rannikko, Jenna (2019-07-31)
Blocking Clever-1 on human monocytes inhibits the growth of aggressive breast cancer
Rannikko, Jenna
(31.07.2019)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2019082625585
https://urn.fi/URN:NBN:fi-fe2019082625585
Tiivistelmä
Immunosuppressive tumor microenvironment limits antitumoral immunity and facilitates cancer progression. Tumor-associated macrophages that are mainly derived from blood monocytes, are central regulators of the tumor immune microenvironment and appealing targets in cancer immunotherapy. A subset of monocytes and macrophages express a scavenger and adhesion receptor Clever-1 that on tumor-associated macrophages promotes immunosuppression, cancer growth and metastasis. Nevertheless, the role of monocyte Clever-1 in cancer is largely unknown. The aim of this thesis was to determine how inhibition of monocyte Clever-1 with a humanized anti-Clever-1 antibody, FP-1305, affects the growth of cancer cells. This was investigated in monocyte-cancer cell co-culture that was followed with live-imaging. Additionally, the binding of FP-1305 on macrophage Clever-1 and the effect of FP-1305 treatment on monocyte function were investigated. Our results show that Clever-1+ monocytes induce the growth of triple-negative breast cancer cells in monocyte co-culture, while treating the monocytes with FP-1305 prevents the co-culture growth. Interestingly, Clever-1+ monocytes did not promote the growth of less aggressive luminal A breast cancer cells. In addition, FP-1305 treatment did not affect the viability of monocytes nor did it affect cancer cell proliferation directly. Immunofluorescence stainings revealed that FP-1305 epitope was more accessible at the adhering surface of macrophages, suggesting that FP-1305 binds to the active form of Clever-1. In conclusion, anti-Clever-1 treatment of human monocytes can suppress the growth of aggressive breast cancer without having undesirable effects on monocyte function. This further supports our previous findings that Clever-1 is an attractive cancer immunotherapy target.