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bioRxiv · 10.1101/2020.10.19.345629

Prioritization prostate cancer to immune checkpoint therapy by ranking tumors along IFN-γ axis and identification of immune resistance mechanisms

Reva, B.·Omelchenko, T.·Calinawan, A. P.·Nair, S.·Schadt, E.·Tewari, A.
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Abstract

We propose priotirization of prostate cancer patients to PD-L1 checkpoint therapy by assessing activity of IFN-{gamma}/PD-L1 signaling in tumor from transcriptional profile. To this end, we introduced a new approach for inferring pathway activity and suppression (IPAS) by assessing significance of positioning pathways genes expression levels at top (activation) or bottom (suppression) in gene expression profile of a given tumor. By ordering tumors along IFN-{gamma}/PD-L1 axis, we determined distinct "IFN-{gamma}-depleted" and "IFN-{gamma}-enriched" immune subtypes, genes involved in immune evasion and potential targets for combination therapy. Using IPAS scoring method, we proposed biomarker panels for accurate ranking tumors along IFN-{gamma}/PD-L1 axis.

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Reva, B., Omelchenko, T., Calinawan, A. P., Nair, S., Schadt, E., Tewari, A.. 2020-10-19. Prioritization prostate cancer to immune checkpoint therapy by ranking tumors along IFN-γ axis and identification of immune resistance mechanisms. https://doi.org/10.1101/2020.10.19.345629

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