Abstract 1500: Understanding tumor cell community and its evolution by single cell analysis in liver cancer
| Autor: | Lichun Ma, Xin Wei Wang, Maria O. Hernandez, Jeremy L. Davis, Yongmei Zhao, David E. Kleiner, Michael C. Kelly, Bradford J. Wood, Bao Tran, Monika Mehta, Kris Ylaya, Stephen M. Hewitt, Zachary Rae, Tim F. Greten, Jonathan M. Hernandez, Sean P. Martin |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:1500-1500 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Tumor cell biodiversity is a major contributing factor to therapeutic failures and lethal outcomes of solid malignancies. Primary liver cancer, comprising mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), is the second most lethal malignancy worldwide. To understand the biodiversity of tumor cell community in liver cancer, we performed single-cell transcriptome profiling of primary HCC and iCCA from 19 patients, who were enrolled at the NIH Clinical Center for immune checkpoint inhibition clinical trials. We found malignant cells differed within and between tumors, indicating both intratumor and intertumor heterogeneity. We developed a method to measure intratumor heterogeneity. Strikingly, the degree of intratumor diversity was associated with patient outcome where tumors with high diversity was associated with poor prognosis while tumors with low diversity was linked to good prognosis. The link between intratumor diversity and patient prognosis was also observed in bulk genomic and transcriptomic profiles for hundreds of HCC as well as iCCA patients. We found a polarization of the diverse landscapes of tumor microenvironment (TME) from low diversity and high diversity tumors. By searching upstream regulators of TME, we found an increased VEGF expression in high diversity tumors linked to diversity-related polarization of stromal and immune cells. Additionally, tumor evolutionary trajectory was uncovered by single-cell transcriptomic profiles generated from tumor biopsies collected from patients at baseline and after treatment with immune checkpoint inhibitors. Our results offer insight into the diverse ecosystem of HCC and iCCA and determine an impact of tumor cell biodiversity on patient prognosis, which may further benefit the prediction of clinical response to immune therapy. Citation Format: Lichun Ma, Maria O. Hernandez, Yongmei Zhao, Monika Mehta, Bao Tran, Michael Kelly, Zachary Rae, Jonathan M. Hernandez, Jeremy L. Davis, Sean P. Martin, David E. Kleiner, Stephen M. Hewitt, Kris Ylaya, Bradford J. Wood, Tim F. Greten, Xin Wei Wang. Understanding tumor cell community and its evolution by single cell analysis in liver cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1500. |
| Databáze: | OpenAIRE |
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