A syngeneic mouse model of metastatic hormone-naive prostate cancer provides a platform for studying combination immunotherapy
Year: 2026
Type: article
Abstract: Metastatic hormone-naive prostate cancer (mHNPC) refers to a small subset of diagnosed prostate tumors and presents very high mortality and poor response to available therapies. Despite its clinical relevance, we lack immunocompetent models that are both androgen-dependent and reliably metastatic, limiting the implementation of translational research strategies. Here we develop and characterize PL051, a syngeneic, bioluminescence tractable prostate carcinoma cell line derived from a Pten / Lkb1 double knockout genetic mouse model that reproducibly engrafts orthotopically in C57BL/6 mice, maintains androgen-receptor (AR) signaling, and consistently disseminates to soft tissues and bone. PL051 preserves Pten / Lkb1 loss and PI3K–AKT activation, shows intact AR responsiveness in vitro, and responds to AR-pathway intensification in vivo. We provide two complementary proof-of-concept evidence for the preclinical potential of this model. On one hand, we show the therapeutic benefit of combining androgen signaling inhibition and anti-PD1 treatment. On the other hand, we provide evidence showing that co-targeting myeloid cells with a CSF1R inhibitor further enhances therapeutic activity of checkpoint blockade by depleting suppressive macrophages and boosting T-cell recruitment. Together, this preclinical model fills a critical gap for studying mHNPC biology and provides a scalable, immune-competent model for testing rational combinatorial treatments.
Source: Cell Death Discovery
Authors: Victoria Cid-Centelles, Jaione Auzmendi-Iriarte, Ianire Astobiza, Onintza Carlevaris, Ivana Rondon-Lorefice, Maria Ponce-Rodriguez, Marc Guiu, Ivana Hermanova, Leire Egia-Mendikute, Saioa Garcia-Longarte, Amaia Ercilla-Eguiarte, Natalia Martin-Martin, Amaia Zabala-Letona, Asis Palazon, Roger R. Gomis, Isabel Mendizabal, Arkaitz Carracedo, Marco Piva
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: AstraZeneca, Fundación BBVA, Ministerio de Ciencia, Innovación y Universidades, Department of Industry, Tourism and Trade, Fundación Científica Asociación Española Contra el Cáncer, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, Agencia Estatal de Investigación
Awards: G1095021113, G1096179202, G1105844351, G121809054, G1470946416, G1855990336, G2309174360, G252646220, G2660406951, G279363373, G3518538256, G4065052777, G4093352487, G4212894969, G430777504, G441729838, G4740006153, G491712853, G5292128943, G5404395142, G5421974903, G5635532810, G5702581365, G593054264, G5936500278, G624877701, G6358814623, G6395704295, G6818958183, G717256432, G7805626310, G7860301950, G7863371703, G833241955, G8497050386, G8920660035, G897484643, G9000277404, G99296377
OpenAlex ID: W7225011048