晚期肾细胞癌中检查点基因表达降低与对纳武利尤单抗-伊匹木单抗联合疗法的原发性耐药相关.pdf

1、Lower Checkpoint Gene Expression is Associated with Primary Resistance to Nivolumab-Ipilimumab Combination in Advanced Renal Cell CarcinomaRana R.McKay1,Adam J.Dugan2,Unnati Jariwala2,Karyn Ronski2,Jacob Mercer2,Eddy Saad3,Jad El Masri3,Marc Machaalani3,Mustafa Saleh3,Cody Rose4,Maxine Sun3,Sabina S

2、ignoretti3,David Braun4,Sumanta Pal5,Toni K.Choueiri31University of California,San Diego,2Tempus AI,Inc.,3Dana Farber Cancer Institute/Harvard Cancer Center,4Yale Cancer Center,5City of Hope Cancer CenterBackground Immunotherapy combinations have emerged as the standard of care for patients with adv

3、anced RCC Nivolumab-ipilimumab is associated with long-term durability,though a subset of patients do not derive any benefit from treatment CheckMate 214 rPFS(ITT)Median Follow-Up 9.3 years CheckMate 214 Best Objective Response ITT RCC=Renal cell carcinoma;rPFS=Radiographic progression-free survival

4、;ITT=Intent to treat.Choueiri et al,ASCO Annual Meeting,2025Rationale and Hypothesis Rationale:Urgent need to identify negative selection markers for treatment with nivolumab-ipilimumabHypothesis:Molecular differences exist among tumors with and without primary progression to nivolumab-ipilimumab Me

5、thods Tempus Lens was used to select records for 106 patients with RCC who received 1L nivolumab-ipilimumab Eligible patients:Tumor samples collected within one year of treatment initiation Processed using xT(DNA-seq)and xR(RNA-seq)assays Treatment response:Investigator-assessed within 90 days of th

6、erapy start Categorized as PD versus non-PD RNA-seq data were normalized,log2-transformed,and batch-corrected Measured checkpoint and angiogenic gene expression(TPM)Immunologic phenotype:TMB(mt/Mb)MSI status PD-L1(IHC,22c3)Immune infiltration estimated by quanTIseq(RNA)RCC=Renal