Imaging-Based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids.

Cancer immunotherapy is used to treat tumors by modulating the immune system. Although the anticancer efficacy of cancer immunotherapy has been evaluated prior to clinical trials, conventional in vivo animal and endpoint models inadequately replicate the intricate process of tumor elimination and reflect human-specific immune systems. Therefore, more sophisticated models that mimic the complex tumor-immune microenvironment must be employed to assess the effectiveness of immunotherapy. Additionally, using real-time imaging technology, a step-by-step evaluation can be applied, allowing for a more precise assessment of treatment efficacy. Here, an overview of the various imaging-based evaluation platforms recently developed for cancer immunotherapeutic applications is presented. Specifically, a fundamental technique is discussed for stably observing immune cell-based tumor cell killing using direct imaging, a microwell that reproduces a confined space for spatial observation, a droplet assay that facilitates cell-cell interactions, and a 3D microphysiological system that reconstructs the vascular environment. Furthermore, it is suggested that future evaluation platforms pursue more human-like immune systems.

Effects of extracellular adhesion molecules on immune cell mediated solid tumor cell killing.

Adoptive cell therapy (ACT) using ex vivo engineered/expanded immune cells demonstrated poor efficacy against solid tumors, despite its great success in treating various hematopoietic malignancies. To improve ACT for solid tumors, it is crucial to comprehend how the numerous components of the tumor microenvironment (TME) surrounding solid tumor cells influence killing ability of immune cells. In this study, we sought to determine the effects of extracellular adhesion provided by extracellular matrix (ECM) of TME on immune cell cytotoxicity by devising microwell arrays coated with proteins either preventing or promoting cell adhesion. Solid tumor cells in bovine serum albumin (BSA)-coated microwells did not attach to the surfaces and exhibited a round morphology, but solid tumor cells in fibronectin (FN)-coated microwells adhered firmed to the substrates with a flat shape. The seeding densities of solid tumor cells and immune cells were tuned to maximize one-to-one pairing within a single microwell, and live cell imaging was performed to examine dynamic cell-cell interactions and immune cell cytotoxicity at a single cell level. Both natural killer (NK) cells and T cells showed higher cytotoxicity against round tumor cells in BSA-coated microwells compared to flat tumor cells in FN-coated microwells, suggesting that extracellular adhesion-mediated firm adhesion of tumor cells made them more resistant to immune cell-mediated killing. Additionally, NK cells and T cells in FN-coated microwells exhibited divergent dynamic behaviors, indicating that two distinct subsets of cytotoxic lymphocytes respond differentially to extracellular adhesion cues during target cell recognition.

Corrigendum: Effects of extracellular adhesion molecules on immune cell mediated solid tumor cell killing.

[This corrects the article DOI: 10.3389/fimmu.2022.1004171.].