Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Abstract

Knowledge about the hematopoietic niche has evolved considerably in recent years, in particular through in vitro analyzes, mouse models and the use of xenografts. Its complexity in the human bone marrow, in particular in a context of hematological malignancy, is more difficult to decipher by these strategies and could benefit from the knowledge acquired on the niches of solid tumors. Indeed, some common features can be suspected, since the bone marrow is a frequent site of solid tumor metastases. Recent research on solid tumors has provided very interesting information on the interactions between tumoral cells and their microenvironment, composed notably of mesenchymal, endothelial and immune cells. This review thus focuses on recent discoveries on tumor niches that could help in understanding hematopoietic niches, with special attention to 4 particular points: i) the heterogeneity of carcinoma/cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs), ii) niche cytokines and chemokines, iii) the energy/oxidative metabolism and communication, especially mitochondrial transfer, and iv) the vascular niche through angiogenesis and endothelial plasticity. This review highlights actors and/or pathways of the microenvironment broadly involved in cancer processes. This opens avenues for innovative therapeutic opportunities targeting not only cancer stem cells but also their regulatory tumor niche(s), in order to improve current antitumor therapies.

The impact of microbially modified metabolites associated with obesity and bariatric surgery on antitumor immunity

“…The efficacy of immunotherapy is closely related to the tumor microenvironment. The tumor microenvironment is a complicated integrated system comprised of tumor cells, tumor-associated fibroblasts, and cytokines ( 108 ) and contains various types of immune cells, including T cells, NK cells, macrophages, and dendritic cells ( 109 ). However, the tumor microenvironment can be altered by tumor cells to enable escape from the immune system.…”

Environmental exposure and the role of AhR in the tumor microenvironment of breast cancer

“…The tumor microenvironment (TME) corresponds to the fact that tumor cells are surrounded in close proximity by a number of non - cancerous cells including cancer associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), adipocytes, myeloid-derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), tumor infiltrating lymphocytes (TILs), and endothelial cells ( Joyce and Pollard 2009 ; Lazennec and Lam 2016 ; Binnewies et al, 2018 ). In addition to direct contact with tumor cells, TME cells will interact with tumor cells though a number of different soluble factors including cytokines and chemokines, which will reshape TME to support cancer initiation, progression, and metastasis ( Ali and Lazennec 2007 ; Lazennec and Richmond 2010 ; Mancini et al, 2021 ) ( Figure 1 ).…”

Ex vivo culture of malignant primary B cells

“…In particular, the presence of a bone-like niche is relevant in 3D models investigating MM, since osteolytic disease is a hallmark of this pathology that researchers have attempted to phenocopy, notably by exploiting 3D mineralized bone models (207). Moreover, although the use of primary (bone marrow) mesenchymal stem/stromal cells rather than cell lines can more accurately model the original TME, their current shaky definition and the variations in associated isolation and culture methods seem antagonistic to the development of a defined and reproducible 3D model (214,215). The generation of (bone marrow) organoids, which are self-organizing and self-renewing microstructures, is a way to partially address these issues (216).…”