Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies
January 12, 2023
Abstract
The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PDL1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the everabundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose protumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.
Source:
Rebecca Adams, Gabriel Osborn, Bipashna Mukhia, Roman Laddach, Zena Willsmore, Alicia Chenoweth, Jenny L C Geh, Alastair D MacKenzie Ross, Ciaran Healy, Linda Barber, Sophia Tsoka, Victoria Sanz-Moreno, Katie E Lacy & Sophia N Karagiannis (2022)
Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies, OncoImmunology, 11:1, 2127284, DOI: 10.1080/2162402X.2022.2127284