Nat commun: heterogeneity of liver cancer cells helps to explain tumor progression in patients

On February 17, 2020, researchers from Sinai Mountain hospital reported that many hepatoma tumors contain highly diversified cell groups, which is called the heterogeneity within the tumor and will significantly affect the growth rate of the tumor The contribution of the immune system to this heterogeneity may have important clinical significance In a new study published in nature communications, the team reported that about 30% of patients with HCC, the most common form of liver cancer, grow rapidly by hijacking different gene networks Image source: https://cn.bing.com "cancer is a complex ecosystem, and our results show for the first time that they can evolve through interaction with the immune system," said Dr Augusto Villanueva, assistant professor of hepatoma program at Tisch Cancer Institute in Mount Sinai and corresponding author of the study "By better understanding the development of tumors, we learned more about how they adapt to pharmacological stress and how they form resistance mechanisms to cancer treatment This greater awareness will hopefully lead us to recognize biomarkers that can predict which patients will respond to treatment "One of the team's findings is that a single liver cancer biopsy may produce a false description of the liver tumor "Some tumors are very similar in terms of genetic makeup and immune cell infiltration, while others are very different," said Dr Villanueva This means that biopsies from the same tumor will generate different information according to the location of the sample, thus affecting the clinical decision-making of patients That's why our work is aimed at understanding how tumors evolve and the different trajectories they can take, which is very important for future cancer research and effective treatment of cancer "As immunotherapy continues to change cancer research and treatment, one of the most promising areas is liver cancer In terms of incidence rate and mortality rate, liver cancer has become the fastest growing malignancy in the United States, with 3.3 new cases per year Two phase 2 clinical trials using PD-1 immunocheckpoint inhibitors have achieved unprecedented responses in humans, prompting the food and Drug Administration (FDA) to accelerate the approval of these drugs for second-line treatment of advanced HCC PD-1 immunocheckpoint inhibitors help the immune system recognize and attack cancer cells Recently, a phase III clinical trial combining PD-1 immunosuppressive checkpoint inhibitors and antiangiogenic drugs improved survival compared with the current first-line treatment standard sorafenib However, only about 30% of HCC patients are considered to have a good response to immunosuppression - a result not uncommon in immunotherapy "The evolution of the immune system has an important constraint on liver cancer By investigating the interaction between immune cells and cancer cells at the molecular level, we try to predict the mechanism of tumor resistance," explained Dr Bojan losic, the first author of the study "Our work is particularly relevant given the significant success of immunocheckpoint inhibitors in some heterogeneous solid tumors "To understand the mechanism driving tumor progression, the team from Mount Sinai and other medical centers around the world conducted a comprehensive molecular analysis of gene expression analysis, immune activity, and DNA mutations in tumor nodules from 14 patients with liver cancer in the same region This study is the first to use single-cell RNA sequencing in multiple regions of the same tumor nodule, and also the first to assess the contribution of the immune system to the evolution of liver cancer Reference: Augusto Villanueva et al Internal ergonomics and internal evolution in lever cancer nature communication 2020 Doi: https://doi.org/10.1038/s41467-019-14050-z