Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Progress of oncolytic virotherapy for neuroblastoma.

As a neuroendocrine tumor derived from the neural crest, neuroblastoma (NB) is the most common extracranial solid tumor in children. The prognosis in patients with low- and intermediate-risk NB is favorable while that in high-risk patients is often detrimental. However, the management of the considerably large proportion of high-risk patients remains challenging in clinical practice. Among various new approaches, oncolytic virus (OV) therapy offers great advantages in tumor treatment, especially for high-risk NB. Genetic modified OVs can target NB specifically without affecting normal tissue and avoid the widespread drug resistance issue in anticancer monotherapy. Meanwhile, its safety profile provides great potential in combination therapy with chemo-, radio-, and immunotherapy. The therapeutic efficacy of OV for NB is impressive from bench to bedside. The effectiveness and safety of OVs have been demonstrated and reported in studies on children with NB. Furthermore, clinical trials on some OVs (Celyvir, Pexa-Vec (JX-594) and Seneca Valley Virus (NTX-010)) have reported great results. This review summarizes the latest evidence in the therapeutic application of OVs in NB, including those generated in cell lines, animal models and clinical trials.