Looking inside the primary tumour: what drives immunotherapy response in renal cell carcinoma?

The introduction of immune checkpoint inhibitors has changed how we treat advanced renal cell carcinoma (RCC). Durable responses, once rare, now occur in a meaningful proportion of patients treated with PD-1–based combinations. Yet, despite these advances, a familiar challenge remains: some tumours respond dramatically while others benefit little. Understanding the biology behind this variability is a major question in kidney cancer research.1 2Most studies of response and resistance mechanisms have examined metastatic lesions or old nephrectomy specimens collected before treatment. However, many patients receiving systemic therapy still have their primary tumour. As neoadjuvant and perioperative immunotherapy strategies grow, it becomes more important to understand how the primary tumour responds.