Protocol for the biofabrication of immunocompetent tumor-on-chip models from patient solid tumors for assessment of anticancer therapies.

We present a protocol to generate immunocompetent 3D tumor-on-chip models from human solid tumors, enabling more accurate therapy response assessment than traditional 2D assays. We outline the isolation and culture of autologous tumor cells, CD8 tumor-infiltrating lymphocytes, and cancer-associated fibroblasts, followed by their encapsulation in a 3D biomimetic matrix within microfluidic devices and subsequent video microscopy. The protocol is adaptable to other tumor types, including breast and colon cancer.

Bioengineering a Patient-Derived Vascularized Lung Tumor-on-Chip Model to Decipher Immunomodulation by the Endothelium.

The endothelium compartment is a key player in tumor initiation and progression, but most existing tumor-on-chip models lack clinical relevance. Here, a 3D vascularized tumor-on-chip (vToC) model, generated with patient-derived microvascular endothelial cells (ECs) that are freshly isolated from surgical lung cancer samples, is presented. The microvessel molecular identity, morphology, and functionality are assessed by transcriptomic, immunofluorescence, TNF-α stimulation, and permeability assays.

Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip.

There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms.

Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway.

Unlabelled: In solid tumors, cancer stem cells (CSCs) or tumor-initiating cells (TICs) are often found in hypoxic niches. Nevertheless, the influence of hypoxia on TICs is poorly understood. Using previously established, TIC-enrichedpatient-derived colorectal cancer (CRC) cultures, we show that hypoxia increases the self-renewal capacity of TICs while inducing proliferation arrest in their more differentiated counterpart cultures.

Hypoxia- and MicroRNA-Induced Metabolic Reprogramming of Tumor-Initiating Cells.

Colorectal cancer (CRC), the second most common cause of cancer mortality in the Western world, is a highly heterogeneous disease that is driven by a rare subpopulation of tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Over the past few years, a plethora of different approaches, aimed at identifying and eradicating these self-renewing TICs, have been described. A focus on the metabolic and bioenergetic differences between TICs and less aggressive differentiated cancer cells has thereby emerged as a promising strategy to specifically target the tumorigenic cell compartment.

Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity.

Cancer stem cells, also known as tumor-initiating cells (TICs), are a population of aggressive and self-renewing cells that are responsible for the initiation and progression of many cancers, including colorectal carcinoma. Intratumoral hypoxia, i.e.

In search of definitions: Cancer-associated fibroblasts and their markers.

The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer-associated fibroblasts (CAFs), a type of perpetually activated fibroblasts, have been implicated to have a strong tumor-modulating effect and play a key role in areas such as drug resistance. Identification of CAFs has typically been carried based on the expression of various "CAF markers", such as fibroblast activation protein alpha (FAP) and alpha smooth muscle actin (αSMA), which separates them from the larger pool of fibroblasts present in the body.

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections.

Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment.