US 12,487,233 B2
Determining functional status of immune cells types and immune response
Anja Van De Stolpe, Vught (NL); Arie Rombertus Van Doorn, Zaltbommel (NL); Wilhelmus Franciscus Johannes Verhaegh, Heusden Gem. Asten (NL); Steven Paulus Lambertus Kuijpers, Veldhoven (NL); Michael Van Hartskamp, Eindhoven (NL); and Hussam Nachabe, Eindhoven (NL)
Assigned to KONINKLIJKE PHILIPS N.V., Eindhoven (NL)
Appl. No. 16/652,555
Filed by KONINKLIJKE PHILIPS N.V., Eindhoven (NL)
PCT Filed Oct. 1, 2018, PCT No. PCT/EP2018/076614
§ 371(c)(1), (2) Date Mar. 31, 2020,
PCT Pub. No. WO2019/068623, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/683,710, filed on Jun. 12, 2018.
Claims priority of provisional application 62/566,755, filed on Oct. 2, 2017.
Prior Publication US 2020/0240979 A1, Jul. 30, 2020
Int. Cl. G01N 33/50 (2006.01); G16B 5/20 (2019.01); G16B 10/00 (2019.01); G16B 20/20 (2019.01); G16B 25/10 (2019.01); G16B 40/00 (2019.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01)
CPC G01N 33/5041 (2013.01) [G01N 33/5091 (2013.01); G16B 5/20 (2019.02); G16B 10/00 (2019.02); G16B 20/20 (2019.02); G16B 25/10 (2019.02); G16B 40/00 (2019.02); G16H 50/20 (2018.01); G16H 50/30 (2018.01); G01N 2800/60 (2013.01); Y10S 706/924 (2013.01)] 3 Claims
OG exemplary drawing
 
1. A method for treating a cancer subject, comprising:
receiving a determined functional status of at least one immune cell type in at least one sample of the cancer subject, wherein the functional status of the at least one immune cell type is based on an inferred activity of at least one signaling pathway in the at least one immune cell type, and wherein the determined functional status of at least one immune cell type in the at least one sample of the cancer subject is an inactive functional status, and wherein the functional status is determined by:
receiving an expression level of one or more target genes of the at least one signaling pathway;
determining an activity level of a signaling pathway associated transcription factor (TF) element, the signaling pathway associated TF element controlling transcription of the three or more target genes, the determining being based on evaluating a calibrated mathematical pathway model relating expression levels of the one or more target genes to the activity level of the at least one signaling pathway, wherein the calibrated mathematical pathway model is a centroid or a linear model, or a Bayesian network model based on conditional probabilities, wherein the calibrated mathematical pathway model is calibrated using a calibration dataset, the calibration dataset comprising measured expression levels of the one or more target genes each associated with a ground truth with respect to a plurality of different possible functional activity statuses of the signaling pathway, the plurality of different possible functional activity statuses comprising at least an inactive functional status and an active functional status, wherein at least some of the measured expression levels of the one or more target genes are associated with a ground truth of an inactive functional status and at least some of the measured expression levels of the one or more target genes are associated with a ground truth of an active functional status;
inferring the activity of the at least one signaling pathway in the at least one immune cell type based on the determined activity level of the signaling pathway associated TF element, wherein the inferred activity of the at least one signaling pathway is an inactive activity; and
determining, based on the inferred inactive activity of at least one signaling pathway, a functional status of at least one immune cell type in the at least one sample of the cancer subject, wherein the determined functional status is an inactive functional status; and
administering, in response to receiving the determined inactive functional status of the at least one immune cell type in the at least one sample of the cancer subject, a cancer therapy to the cancer subject, wherein the administered therapy is immunotherapy, chemotherapy, and/or radiation therapy.