Determinants, mechanisms, and functional outcomes of myeloid cell diversity in cancer

Abstract

The tumor microenvironment (TME) is a complex architecture of cells, including those of the immune system, of matrix components, and of their interactions within the unique physical traits of the cancer tissue. 1,2 Many elements influence the composition and cellular dynamics of the TME, such as the anatomical site, the type, and stage of the disease, the therapeutic regimen as well as host factors like age, sex, and comorbidities. 2 Within the extreme diversity of TMEs, parameters integrating the relative composition, spatial arrangement, and functional properties of infiltrating immune cells are useful indicators of disease progression and response to therapies. 2,3 For instance, high tumor infiltration of cytotoxic CD8 + T cells engaging inhibitory crosstalk in the TME via the programmed death (PD)1:PD-L1/PD-L2 axis often predicts efficient response to immune checkpoint blockade therapy. 3 In some cases, CD8 + T cells form organized assemblies with antigen-presenting cells such as dendritic cells (DCs), B cells, and macrophages within the tumor stroma; these so-called tertiary lymphoid structures are considered sites of efficient T-cell priming, and their presence is associated with good response to immunotherapy. 4 In this context, a subset of conventional DCs, termed cDC1, can efficiently cross-present tumor antigens for the induction of a durable immune response. 5-7 Accumulation of cDC1 at the tumor site is mediated at least in part by chemokines released by infiltrating natural killer (NK) cells, 8 a

The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development

“…[8][9][10] TAMs usually exhibit the properties of M2-like macrophages in TME and are involved directly or indirectly in tumor progression. [11][12][13] As TAMs are a dynamic population of cells, switching TAMs toward an antitumor phenotype may provide an opportunity to reshape the immunosuppressive TME and restrain the development of cancers. Despite recent progress in preclinical and clinical studies, there are still some unanswered questions.…”

Tumor microenvironment signaling and therapeutics in cancer progression

“…For instance, DCs secrete the chemoattractants chemokine (C‐X‐C motif) ligand 9 (CXCL9) and 10 (CXCL10) to facilitate the infiltration of CD8 + T eff cells in the TME and for T cell cytotoxic activity [ 15 ]. Instead, their engagement in inhibitory crosstalk, such as with the PD‐1/ programmed death‐ligand 1 (PD‐L1) signaling axis, leads to immunosuppression in the TME [ 16 ]. Other immune cells facilitating a pro‐tumorigenic response in the TME include the immunomodulatory regulatory T (T reg ) cells and the myeloid suppressor (MDSCs) that result in an immunosuppressive TME [ 17 ] and therapy failure.…”

A PGE2-MEF2A axis enables context-dependent control of inflammatory gene expression

“…PGE 2 has complex immune-regulatory properties that include cell recruitment and vasodilation, elicitation of regulatory programs in leukocytes, and inhibition of cytotoxic responses ( Hangai et al., 2016 ; Luan et al., 2015 ; Perkins et al., 2018 ; Rodríguez-Ubreva et al., 2017 ; Sanin et al., 2018 ). PGE 2 is a driver of immune modulation in the tumor microenvironment ( Caronni et al., 2021 ), and blockade of this molecule is a target of combinatorial immunotherapies ( Böttcher et al., 2018 ; Hou et al., 2016 ; Veglia et al., 2019 ; Zelenay et al., 2015 ). Along the same line, key immune modulators, such as interleukin-10 (IL-10) or IL-4, are essential for tissue homeostasis but may also dampen anti-tumor immunity ( Ip et al., 2017 ; Maier et al., 2020 ; Minutti et al., 2017 ; Saraiva et al., 2020 ).…”