In vivo CRISPR screens identify<i>Mga</i>as an immunotherapy target in triple-negative breast cancer
Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic tumor models, we identified core and context-dependent immune evasion pathways across cancer types. This valuable high-confidence dataset is available for the further understanding of tumor intrinsic immunomodulators, which may lead to the discovery of effective anticancer therapeutic targets. With a focus on triple-negative breast cancer (TNBC), we found that <i>Mga</i> knock-out significantly enhances antitumor immunity and inhibits tumor growth. Transcriptomics and single-cell RNA sequencing analyses revealed that Mga influences various immune-related pathways in the tumor microenvironment. Our findings suggest that Mga may play a role in modulating the tumor immune landscape, though the precise mechanisms require further investigation. Interestingly, we observed that low MGA expression in breast cancer patients correlates with a favorable prognosis, particularly in those with active interferon-γ signaling. These observations provide insights into tumor immune escape mechanisms and suggest that further exploration of MGA's function could potentially lead to effective therapeutic strategies in TNBC.
Authors
- Litong Nie (ORCID: https://orcid.org/0000-0002-0326-4517)
- Jae‐Il Park (ORCID: https://orcid.org/0000-0002-0737-2654)
- Kuirong Jiang (ORCID: https://orcid.org/0000-0002-2849-5450)
- Feng Xu (ORCID: https://orcid.org/0000-0001-6888-8753)
- Traver Hart (ORCID: https://orcid.org/0000-0002-1880-3341)
- Lori Wilson (ORCID: https://orcid.org/0000-0001-5453-9077)
- Dadi Jiang (ORCID: https://orcid.org/0000-0002-0935-3908)
- Ling Yin (ORCID: https://orcid.org/0000-0003-1606-2620)
- Dan Su
- Chang Yang (ORCID: https://orcid.org/0000-0001-6678-3659)
- Mengfan Tang (ORCID: https://orcid.org/0000-0002-6552-6762)
- Siting Li (ORCID: https://orcid.org/0000-0002-8292-1393)
- Junjie Chen (ORCID: https://orcid.org/0000-0002-1493-2189)
- Huimin Zhang (ORCID: https://orcid.org/0000-0002-5359-1399)
- Chao Wang (ORCID: https://orcid.org/0009-0001-3192-253X)
- Jie Zhang (ORCID: https://orcid.org/0000-0002-1397-5224)
- Zhen Chen (ORCID: https://orcid.org/0000-0003-1603-4638)
- Yuanjian Huang (ORCID: https://orcid.org/0000-0002-1611-8252)
- Dandan Zhu
- Shimin Wang (ORCID: https://orcid.org/0000-0002-3713-8738)
- Min Huang (ORCID: https://orcid.org/0000-0002-8567-990X)
- Shengzhe Zhang
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Harbin Medical University (CN)
- Third Affiliated Hospital of Harbin Medical University (CN)
- Jiangsu Province Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1073/pnas.2406325121
- Citations
- 6
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 1.44
Funders
- Cancer Prevention and Research Institute of Texas
- University of Texas Health Science Center at Houston
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- National Cancer Institute