The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity
dc.contributor.author | Lukhele, Sabelo | |
dc.contributor.author | Rabbo, Diala Abd | |
dc.contributor.author | Guo, Mengdi | |
dc.contributor.author | Shen, Jian | |
dc.contributor.author | Elsaesser, Heidi J. | |
dc.contributor.author | Quevedo, Rene | |
dc.contributor.author | Carew, Madeleine | |
dc.contributor.author | Gadalla, Ramy | |
dc.contributor.author | Snell, Laura M. | |
dc.contributor.author | Mahesh, Lawanya | |
dc.contributor.author | Ciudad, M. Teresa | |
dc.contributor.author | Snow, Bryan E. | |
dc.contributor.author | You-Ten, Annick | |
dc.contributor.author | Haight, Jillian | |
dc.contributor.author | Wakeham, Andrew | |
dc.contributor.author | Ohashi, Pamela S. | |
dc.contributor.author | Mak, Tak W. | |
dc.contributor.author | Cui, Weiguo | |
dc.contributor.author | McGaha, Tracy L. | |
dc.contributor.author | Brooks, David G. | |
dc.contributor.department | Microbiology and Immunology, School of Medicine | |
dc.date.accessioned | 2024-04-24T18:45:08Z | |
dc.date.available | 2024-04-24T18:45:08Z | |
dc.date.issued | 2022-12-13 | |
dc.description.abstract | Type I and II interferons (IFNs) stimulate pro-inflammatory programs that are critical for immune activation, but also induce immune-suppressive feedback circuits that impede control of cancer growth. Here, we sought to determine how these opposing programs are differentially induced. We demonstrated that the transcription factor interferon regulatory factor 2 (IRF2) was expressed by many immune cells in the tumor in response to sustained IFN signaling. CD8+ T cell-specific deletion of IRF2 prevented acquisition of the T cell exhaustion program within the tumor and instead enabled sustained effector functions that promoted long-term tumor control and increased responsiveness to immune checkpoint and adoptive cell therapies. The long-term tumor control by IRF2-deficient CD8+ T cells required continuous integration of both IFN-I and IFN-II signals. Thus, IRF2 is a foundational feedback molecule that redirects IFN signals to suppress T cell responses and represents a potential target to enhance cancer control. | |
dc.eprint.version | Author's manuscript | |
dc.identifier.citation | Lukhele, S., Rabbo, D. A., Guo, M., Shen, J., Elsaesser, H. J., Quevedo, R., Carew, M., Gadalla, R., Snell, L. M., Mahesh, L., Ciudad, M. T., Snow, B. E., You-Ten, A., Haight, J., Wakeham, A., Ohashi, P. S., Mak, T. W., Cui, W., McGaha, T. L., & Brooks, D. G. (2022). The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity. Immunity, 55(12), 2369-2385.e10. https://doi.org/10.1016/j.immuni.2022.10.020 | |
dc.identifier.uri | https://hdl.handle.net/1805/40194 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.immuni.2022.10.020 | |
dc.relation.journal | Immunity | |
dc.rights | Publisher Policy | |
dc.source | Publisher | |
dc.subject | interferon regulatory factor 2 | |
dc.subject | IRF2 | |
dc.subject | type I interferon | |
dc.subject | interferon gamma | |
dc.subject | CD8+ T cells | |
dc.subject | T cell exhaustion | |
dc.subject | immunotherapy | |
dc.subject | adoptive cell transfer | |
dc.subject | CyTOF | |
dc.title | The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity | |
dc.type | Article |