Organoid Models for Precision Cancer Immunotherapy.

Cancer immunotherapy is exploited for the treatment of disease by modulating the immune system. Since the conventional in vivo animal and 2D in vitro models insufficiently recapitulate the complex tumor immune microenvironment (TIME) of the original tumor. In addition, due to the involvement of the immune system in cancer immunotherapy, more physiomimetic cancer models, such as patient-derived organoids (PDOs), are required to evaluate the efficacy of immunotherapy agents. On the other hand, the dynamic interactions between the neoplastic cells and non-neoplastic host components in the TIME can promote carcinogenesis, tumor metastasis, cancer progression, and drug resistance of cancer cells. Indeed, tumor organoid models can properly recapitulate the TIME by preserving endogenous stromal components including various immune cells, or by adding exogenous immune cells, cancer-associated fibroblasts (CAFs), vasculature, and other components. Therefore, organoid culture platforms could model immunotherapy responses and facilitate the immunotherapy preclinical testing. Here, we discuss the various organoid culture approaches for the modeling of TIME and the applications of complex tumor organoids in testing cancer immunotherapeutics and personalized cancer immunotherapy.

Preclinical tumor organoid models in personalized cancer therapy: Not everyone fits the mold.

In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology.

Roles of lncRNAs in cancer: Focusing on angiogenesis.

Approximately 98% of the human genome consists of non-coding sequences that are classified into two classes by size: small non-coding RNAs (≤200 nucleotides) and long non-coding RNAs (≥200 nucleotides). Long non-coding RNAs (lncRNAs) are involved in various cellular events and act as guides, signals, decoys, and dynamic scaffolds. Due to their oncogenic and tumor suppressive roles, lncRNAs are important in cancer development and growth. LncRNAs play their roles by modulating cancer hallmarks, including DNA damage, metastasis, immune escape, cell stemness, drug resistance, metabolic reprogramming, and angiogenesis. Angiogenesis is vital for solid tumors which guarantees their growth beyond 2 mm3. Tumor angiogenesis is a complex process and is regulated through interaction between pro-angiogenic and anti-angiogenic factors within the tumor microenvironment. There are accumulating evidence that different lncRNAs regulate tumor angiogenesis. In this paper, we described the functions and mechanisms of lncRNAs in tumor angiogenesis.