TY - JOUR
T1 - Single-cell CRISPR immune screens reveal immunological roles of tumor intrinsic factors
AU - Hou, Jiakai
AU - Liang, Shaoheng
AU - Xu, Chunyu
AU - Wei, Yanjun
AU - Wang, Yunfei
AU - Tan, Yukun
AU - Sahni, Nidhi
AU - McGrail, Daniel J.
AU - Bernatchez, Chantale
AU - Davies, Michael
AU - Li, Yumei
AU - Chen, Rui
AU - Yi, S. Stephen
AU - Chen, Yiwen
AU - Yee, Cassian
AU - Chen, Ken
AU - Peng, Weiyi
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of NAR Cancer.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance.
AB - Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance.
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U2 - 10.1093/narcan/zcac038
DO - 10.1093/narcan/zcac038
M3 - Article
C2 - 36518525
AN - SCOPUS:85145355632
SN - 2632-8674
VL - 4
JO - NAR Cancer
JF - NAR Cancer
IS - 4
M1 - zcac038
ER -