Renal cell carcinoma (RCC) samples with higher entropy, a measure of evenness and diversity, were associated with favorable prognosis, a study presented at the 2016 Genitourinary Cancers Symposium in San Francisco, CA has shown.1
Because previous research has demonstrated an inverse association between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway, suggesting that T-cell repertoires may affect response to VEGFR inhibition, researchers sought to evaluate the association between T cell repertoire and clinical outcomes in patients with RCC receiving frontline pazopanib.
For the study, researchers analyzed pre-treatment RCC tumors from a phase 3 study of patients with metastatic RCC who were randomly assigned to receive pazopanib 800 mg daily or placebo for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. TCR clonality, a measure of total repertoire represented by expanded clones, and entropy were assessed, as well as programmed death-ligand 1 (PD-L1) expression levels.
Results showed that TCRB and TCRG entropy were highly correlated, and placebo-treated samples with higher TCRG entropy were associated with improved median progression-free survival compared with those with lower TCRG entropy (12.8 months vs 3.1 months; P = .023). Researchers observed a similar trend for samples with TCRB entropy.
In contrast, researchers found no association between entropy or clonality and maximal reduction in tumor volume or PD-L1 expression levels.
“Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study,” the authors concluded.
Ho TH, Gagnon RC, Liu Y, et al. T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade. J Clin Oncol. 2016; 34 (suppl 2S; abstr 501).