On the Biology and Therapeutic Modulation of Macrophages and Dendritic Cells in Cancer

Abstract

Myeloid cells represent a dominant cellular compartment of tumor lesions and play key roles in tumor inception, progression, metastasis, and response to treatment. Mononuclear phagocytes (MNPs), which include dendritic cells and macrophages, are unique among myeloid cells, as they not only shape both the broader composition and state of the tumor microenvironment but can also specifically instruct cancer-specific, T cell–mediated tumor cell killing, making them especially attractive targets for cancer treatment. Although MNPs remain difficult to modulate therapeutically, our understanding of MNP biology in the antitumor immune response has expanded significantly, offering hope for new possibilities in cancer immunotherapy. Here, we review the recent advances in our study of the cellular identity, molecular diversity, and spatial organization of MNPs in tumors, and we discuss the importance of tailoring therapeutic strategies to incorporate these new insights into cancer treatment design. Expected final online publication date for the Annual Review of Cancer Biology, Volume 7 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Explainable Machine Learning Reveals the Role of the Breast Tumor Microenvironment in Neoadjuvant Chemotherapy Outcome

“…It should be noted that we discovered that monocytes, DCs and macrophages play a central role in the response to NAC in breast tumors. These findings align with the emerging paradigm that emphasizes the importance of mononuclear phagocytes (MNPs) in the immune microenvironment, as well as in the activation and functionality of T cells [30, 76].…”

“…As the difference in abundance of subsets fails to provide an explanation, we propose that DCs play distinct roles in the TME depending on tumor subtypes. The functionality of DCs is highly context-dependent and their impact is influenced by their proximity to other cells [29][30][31][32]. For example, in Esophageal cancer, it's not the sheer number of DCs but their proximity to epithelial cells (ECs) that impacts survival [33].…”

The cell stress and immunity cycle in cancer: Toward next generation of cancer immunotherapy

“…The TME tends to undergo multidimensional dysregulation starting from the early stages of tumor development within the organ of origin up to the late stages of progression, co-characterized by metastatic dissemination to distant organ systems. 5 TME is broadly composed of various stromal cells like fibroblasts and the vasculature, and a plethora of primarily myeloid immune cells and relatively less abundant adaptive immune cells. 44 Herein, the immune cells may represent a non-homogeneous mixture between resident immune cells (largely originating from the tumor's organ of origin) and immune cells recruited from circulation.…”

“…However, a more antigenicity-dependent qualitative perspective for the TiME also needs to be taken into consideration (Figure 2) that is, even within the category of immune-rich TME, there might still be more qualitative subcategories distinguished by their antigenicity that is, "canonical T cell hot" TME versus "pseudo-T cell hot" TME. 5 Herein, canonical T cell hot TME might be defined as an immunerich TME that also enriches for high-to-medium TAA/TSA burdens thereby making them truly immunogenic from both quantitative and qualitative perspective. 55 However, within this category, the pseudo-T cell hot tumors represent a clinically relevant paradox.…”

“…The TME is a complex, heterogeneous structure composed of a variety of cell populations and extracellular matrix components that together sustain a dysregulated cellular stress‐immunity cycle. The TME tends to undergo multidimensional dysregulation starting from the early stages of tumor development within the organ of origin up to the late stages of progression, co‐characterized by metastatic dissemination to distant organ systems 5 . TME is broadly composed of various stromal cells like fibroblasts and the vasculature, and a plethora of primarily myeloid immune cells and relatively less abundant adaptive immune cells 44 .…”