Abstract IA16: The complexities of tumor associated macrophages and the key to effective targeting for anti-cancer therapy


 Macrophages are an innate immune cell that play a critical role in host defense and maintaining tissue homeostasis, however their infiltration into tumors has been associated with disease progression and resistance to therapy. Tumor associated macrophages (TAMs) represent a significant proportion of solid tumors, including breast cancer. TAMs play a major role in tumorigenesis as they can enhance tumor cell growth, angiogenesis and metastasis. In addition, TAMs can inhibit anti-tumor responses of T cells. Our recent work has shown that removal or conversion of TAMs to an anti-tumor phenotype enhances chemo- and immuno-therapy establishing TAMs as targets for anti-cancer therapy. We recently revealed that a Class II HDAC inhibitor can polarize TAMs to an anti-tumor phenotype to facilitate reduction in primary and metastatic tumor burden. In addition, we have found that some types of therapy such as poly(ADP-ribose) polymerase (PARP) inhibition (PARPi) can drive development of highly suppressive TAMs, restricting anti-tumor T cell function and survival. Murine models demonstrate that in the absence of TAMs, PARPi induce a robust recruitment of cytotoxic T cells and durable antitumor responses. Therefore, targeting TAMs is a promising strategy for improving PARPi treatment efficacy. However, while there is an urgent need to target TAMs during tumorigenesis and cancer therapy, to date, failure to fully characterize TAM biology and classify multiple subsets has hindered advancement in therapeutic targeting. Deep analysis of TAMs in solid tumors has revealed the complexity of TAMs and revealed major gaps in our knowledge of the functional and phenotypic characterization of TAM subsets associated with cancer, before and after treatment. Here we will discuss the complexity of TAMs in solid tumors including characterizing TAM subsets, location, and crosstalk with neighboring cells, as well as novel TAM-modulating strategies and combinations that are likely to enhance current therapies and overcome chemo- and immuno-therapy resistance.
 Citation Format: Jennifer L Guerriero. The complexities of tumor associated macrophages and the key to effective targeting for anti-cancer therapy [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr IA16.