ArticleCancer immunology, immunotherapy : CII2017
An unbiased in vivo functional genomics screening approach in mice identifies novel tumor cell-based regulators of immune rejection.
Article in Cancer immunology, immunotherapy : CII, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- TGF-β signaling and tumor microenvironment dynamics in bladder cancer progression post-BCG therapy: a longitudinal single-nucleus RNA-seq study.BMC cancer · 2025Article
- Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers.Frontiers in molecular biosciences · 2023Article
- Impaired CXCL12 signaling contributes to resistance of pancreatic cancer subpopulations to T cell-mediated cytotoxicity.Oncoimmunology · 2022Article
- CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes.The Journal of experimental medicine · 2021Article
- Combined RNA/tissue profiling identifies novel Cancer/testis genes.Molecular oncology · 2021Article
- Immunotherapy for triple-negative breast cancer: A molecular insight into the microenvironment, treatment, and resistance.Journal of the National Cancer Center · 2021Review
- Laboratory Models for Investigating Breast Cancer Therapy Resistance and Metastasis.Frontiers in oncology · 2021Review
- IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils.Cancer research · 2020Article
- RNA interference screening methods to identify proliferation determinants and mechanisms of resistance to immune attack.Methods in enzymology · 2020Article
- High expression of CD47 in triple negative breast cancer is associated with epithelial-mesenchymal transition and poor prognosis.Oncology letters · 2019Article
- Functional genomics: paving the way for more successful cancer immunotherapy.Briefings in functional genomics · 2019Review
- Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity.Antibodies (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack. Utilizing this approach in a syngeneic triple-negative breast cancer (TNBC) model, we identified 709 genes that selectively regulated adaptive anti-tumor immunity and focused on five genes (CD47, TGFβ1, Sgpl1, Tex9 and Pex14) with the greatest impact. We validated the mechanisms that underlie the immune-related effects of expression of these genes in different TNBC lines, as well as tandem synergistic interactions. Furthermore, we demonstrate the impact of different genes with previously unknown immune functions (Tex9 and Pex14) on anti-tumor immunity. Thus, this innovative approach has utility in identifying unknown tumor-specific regulators of immune recognition in multiple settings to reveal novel targets for future immunotherapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.