![]() Philadelphia (PA): AACR Cancer Res 2022 82(12_Suppl):Abstract nr 5641. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022 2022 Apr 8-13. Tumor cell intrinsic factors in colorectal cancer immune evasion. Furthermore, the functional role of these immune suppressive genes will be characterized using shAKPS mutant organoids and in vivo orthotopic CRC tumor models.Ĭitation Format: Dechen Wangmo, Xianda Zhao, Angelo Yuan, Travis Gates, Subree Subramanian. Our findings suggest that overexpression of immune suppressive genes in cancer cells may cause T cell dysfunction and exclusion in tumors. Our results show that these immune suppressive genes are overexpressed in tumor tissues, and negatively correlate with CD8 + T cell infiltration. Furthermore, we performed correlation tests to determine their role in immune cell infiltration and T cell dysfunction. To define their expression profile in the tumor, we performed TCGA data analysis in fourteen different cancer types. Using CRISPR/Cas9 screening and integrative immune score analysis, we identified potential immune evasive genes. The shAKPS tumoroids present key features of advanced CRC that are unresponsive to ICIs including invasive tumor, metastasis, and T cell exclusion. Addition of p53 -/- and Smad4 -/- mutations drives invasiveness and metastasis. Cancer immunotherapy microRNAs cancer genetics sarcoma colon cancer. We demonstrated that tumoroids with only shApc and Kras G12D mutations can form a solid tumor in two weeks. Professor, Department of Surgery, University of Minnesota. Therefore, we developed a tumor organoid (tumoroids) model system adapted from Jacks lab that harbors shApc, Kras G12D, p53 -/- and Smad4 -/- (shAKPS) mutations, which are co-mutated with high frequency and associated with poor prognosis. ![]() To elucidate the factors underlying ICI resistance, it is critical that preclinical models faithfully recapitulate the tumor physiology and genetics of the human disease. We hypothesize that targeting tumor-cell intrinsic factors can overcome T cell exclusion and will sensitize the tumor to ICIs. Therefore, it is crucial to characterize factors shaping immune evasion to improve the response to ICIs. However, most CRC lacks robust T-cell infiltration due to immune evasion mechanisms. ICIs preferentially have robust responses from tumors with pre-existing T cell infiltration. In the past decade, immune checkpoint inhibitors (ICIs) have been a major clinical breakthrough with promising clinical benefits in many cancer types, but its efficacy is limited in most (~85%) CRC patients. Although early detection through screening has reduced CRC incidence, the prognosis for metastatic CRC is poor. ![]() The poor response of most colorectal cancer (CRC) patients to immunotherapy is a major unmet clinical need.
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