The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Androgen receptor activity in T cells limits checkpoint blockade efficacy
Open accessAbstract
Immune checkpoint blockade has revolutionized the field of oncology, inducing durable anti-tumour immunity in solid tumours. In patients with advanced prostate cancer, immunotherapy treatments have largely failed1–5. Androgen deprivation therapy is classically administered in these patients to inhibit tumour cell growth, and we postulated that this therapy also affects tumour-associated T cells. Here we demonstrate that androgen receptor (AR) blockade sensitizes tumour-bearing hosts to effective checkpoint blockade by directly enhancing CD8 T cell function. Inhibition of AR activity in CD8 T cells prevented T cell exhaustion and improved responsiveness to PD-1 targeted therapy via increased IFNγ expression. AR bound directly to Ifng and eviction of AR with a small molecule significantly increased cytokine production in CD8 T cells. Together, our findings establish that T cell intrinsic AR activity represses IFNγ expression and represents a novel mechanism of immunotherapy resistance. . Androgen-receptor blockade can overcome immunotherapy resistance in prostate cancer by intrinsically enhancing T cell function and IFNγ responses.
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PD-1 blockade induces responses by inhibiting adaptive immune resistance
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Sex differences in immune responses
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IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
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Genomic correlates of response to CTLA-4 blockade in metastatic melanoma
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Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
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Cited by
Immune checkpoint therapy—current perspectives and future directions
Sharma, P., Goswami, S., Raychaudhuri, D., Siddiqui, B. A., Singh, P., Nagarajan, A., Liu, J., Subudhi, S. K., Poon, C., Gant, K. L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.006 · Cited by 1,206
Gene regulatory network inference in the era of single-cell multi-omics
Badia-i-Mompel, P., Wessels, L., Müller-Dott, S., Trimbour, R., Ramirez Flores, R. O., Argelaguet, R., & Saez-Rodriguez, J. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00618-5 · Cited by 469
Müller-Dott, S., Tsirvouli, E., Vazquez, M., Ramirez Flores, R. O., Badia-i-Mompel, P., Fallegger, R., Türei, D., Lægreid, A., & Saez-Rodriguez, J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad841 · Cited by 380
Tumor cell plasticity in targeted therapy-induced resistance: Mechanisms and new strategies
Shi, Z.-D., Pang, K., Wu, Z.-X., Dong, Y., Hao, L., Qin, J.-X., Wang, W., Chen, Z.-S., & Han, C.-H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01383-x · Cited by 256
RISING STARS: androgens and immune cell function
Ainslie, R. J., Simitsidellis, I., Kirkwood, P. M., & Gibson, D. A. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0398 · Cited by 48
Metadata
- Authors
- Guan, X., Polesso, F., Wang, C., Sehrawat, A., Hawkins, R. M., Murray, S. E., Thomas, G. V., Caruso, B., Thompson, R. F., Wood, M. A., Hipfinger, C., Hammond, S. A., Graff, J. N., Xia, Z., & Moran, A. E.
- Venue
- Nature
- Published
- 2022-03-23
- Volume
- 606
- Issue
- 7915
- Pages
- 791-796
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4220826761
- Cited by
- 391
- References
- 70
- FWCI
- 29.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Guan, X., Polesso, F., Wang, C., Sehrawat, A., Hawkins, R. M., Murray, S. E., Thomas, G. V., Caruso, B., Thompson, R. F., Wood, M. A., Hipfinger, C., Hammond, S. A., Graff, J. N., Xia, Z., & Moran, A. E. (2022). Androgen receptor activity in T cells limits checkpoint blockade efficacy. Nature. https://doi.org/10.1038/s41586-022-04522-6
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