Autophagy Inhibition via Targeting of PIKfyve Potentiates Immune Checkpoint Blockade in Prostate Cancer Therapy

To understand the tumor microenvironment changes in terms of transcriptome upon PIKfyve inhibition by small molecule ESK981 and the immune checkpoint inhibitor anti-PD-1 in Myc-CaP syngeneic mouse model. Overall design: Myc-CaP cells were injected into FVB male mice subcutaneously on both flanks. When tumors reached 50 mm3, mice were randomized and treated with 15 mg/kg ESK981 or vehicle at 5 days per week by oral gavage, while anti-PD-1 or isotype control were given at 200 µg per mouse 3 times per week by intraperitoneal injection. Tumors were collected after 3 weeks of treatment, and total RNA was extracted by QIAGEN RNA extraction kit, and library was prepared by RiboErase selection kit. RNA-sequencing was performed on the Illumina HiSeqTM 2500 platform.