3D models in the new era of immune oncology: focus on T cells, CAF and ECM

Abstract

Immune checkpoint inhibitor therapy has changed clinical practice for patients with different cancers, since these agents have demonstrated a significant improvement of overall survival and are effective in many patients. However, an intrinsic or acquired resistance frequently occur and biomarkers predictive of responsiveness should help in patient selection and in defining the adequate treatment options. A deep analysis of the complexity of the tumor microenvironment is likely to further advance the field and hopefully identify more effective combined immunotherapeutic strategies. Here we review the current knowledge on tumor microenvironment, focusing on T cells, cancer associated fibroblasts and extracellular matrix. The use of 3D cell culture models to resemble tumor microenvironment landscape and to screen immunomodulatory drugs is also reviewed.

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine

“…Immune cells are the major cellular component of the tumor microenvironment and strongly impact prognosis and response to the therapies. 65 However, the impact of hematopoietic and immune cells, as the critical components of the tumor niche, on the tumor in 3D model is poorly understood. Ando et al fabricated a 3D tumor model that recapitulates the hypoxic microenvironment of cancer.…”

Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma

“…The plethora of rodent xenograft models available for preclinical investigation often lack a fully functioning immune system or a completely relevant human tumor microenvironment (TME), and thus fail to accurately capture the complexities and behaviors of human solid tumors (5). New approaches to the evaluation of patient-derived tumor explants, slices, organoids, and spheroids may partially address this issue (6,7). However, all of these require some degree of laboratory manipulation and all lack access to physiological influences only present in the cancer patient including, but not limited to, human circulation and metabolism.…”

Photoacoustic imaging of cells in a three-dimensional microenvironment

“…Moreover, cells inhabiting a rigid surface without a 3D elastic fibrous meshwork (i.e., the extracellular matrix [ECM]) cannot normally response the physical or biochemical cues from the surrounding physiological matrix substrate [1][2][3][4][5]. Recently, in efforts to target the tumor microenvironment for improving both the effectiveness and efficiency of cancer therapeutics, several studies such as immunotherapy, tumor vasculature, or ECM remodeling has been led to a new era and yielded novel insights [6][7][8]. For example, extravasated T lymphocytes infiltrated into the stromal ECM for migrating to the targeted tumor sites has been demonstrated in 3D cell culture models [9][10][11].…”