Androgen receptor activity inversely correlates with immune cell infiltration and immunotherapy response across multiple cancer lineages

Hu, Y.-M.; Zhao, F.; Graff, J.; Chen, C.; Zhao, X.; Thomas, G. V.; Wu, H.; Kardosh, A.; Mills, G.; Alumkal, J.; Moran, A. E.; Xia, Z.

doi:10.1101/2024.05.08.593181

bioRxiv · 10.1101/2024.05.08.593181

Androgen receptor activity inversely correlates with immune cell infiltration and immunotherapy response across multiple cancer lineages

Hu, Y.-M.·Zhao, F.·Graff, J.·Chen, C.·Zhao, X.·Thomas, G. V.·Wu, H.·Kardosh, A.·Mills, G.·Alumkal, J.·Moran, A. E.·Xia, Z.

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Abstract

There is now increasing recognition of the important role of androgen receptor (AR) in modulating immune function. To gain a comprehensive understanding of the effects of AR activity on cancer immunity, we employed a computational approach to profile AR activity in 33 human tumor types using RNA-Seq datasets from The Cancer Genome Atlas. Our pan-cancer analysis revealed that the genes most negatively correlated with AR activity across cancers are involved in active immune system processes. Importantly, we observed a significant negative correlation between AR activity and IFN{gamma} pathway activity at the pan-cancer level. Indeed, using a matched biopsy dataset from subjects with prostate cancer before and after AR-targeted treatment, we verified that inhibiting AR enriches immune cell abundances and is associated with higher IFN{gamma} pathway activity. Furthermore, by analyzing immunotherapy datasets in multiple cancers, our results demonstrate that low AR activity was significantly associated with a favorable response to immunotherapy. Together, our data provide a comprehensive assessment of the relationship between AR signaling and tumor immunity.

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Hu, Y.-M., Zhao, F., Graff, J., Chen, C., Zhao, X., Thomas, G. V., Wu, H., Kardosh, A., Mills, G., Alumkal, J., Moran, A. E., Xia, Z.. 2024-05-14. Androgen receptor activity inversely correlates with immune cell infiltration and immunotherapy response across multiple cancer lineages. https://doi.org/10.1101/2024.05.08.593181

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