Project description:Immune checkpoint blockade is a powerful oncologic treatment modality for a wide variety of human malignancies. Randomized clinical trials are assessing how best to interdigitate this treatment modality with traditional therapies including radiotherapy. A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities including radiotherapy. Here, we demonstrate that radiotherapy induces tumor cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor cell ferroptosis. Mechanistically, IFN derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically repress SLC7A11, a unit of the glutamate-cystine antiporter xc-, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy.
Project description:Radiotherapy is essential to treat colorectal cancer (CRC) although the tolerance of which is of quite common occurrence in clinic. Long noncoding RNA (lncRNA) and circular RNA (circRNAs) have an important role in the radio-resistance of CRC through regulating targeted genes or proteins expression at either transcriptional or post-translational levels. In this study, we aimed to seek out novel lncRNAs and circRNAs involved in radio-resistance by RNA-seq analysis of 8 radiosensitive and 8 radioresistant CRC patients.
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and is a heterogeneous disease, with differences between cancer in the right colon, left colon, and rectum. In this study, plasma samples from CRC patients with varying stage (II or III), primary tumor location (right colon, left colon, or rectum) and survival (survived or died due to CRC) were studied with quantitative label-free proteomics using ultra-definition MSE. Patients were also divided into subgroups based on preoperative radiotherapy status and gender. Further analysis subsequently identified multiple plasma proteins whose expression differed depending on tumor stage, location, patient survival, preoperative radiotherapy status, or gender.
