Metabolic Factors Linked to RCC Treatment Resistance

This article originally appeared here.
Research results provide potential new targets for combination therapy regimens.
Research results provide potential new targets for combination therapy regimens.

HealthDay News — Tumor cell-intrinsic metabolic factors may contribute to anti-programmed death 1 (PD-1)/PD-L1 treatment resistance in renal cell carcinoma (RCC), according to a study published online August 4 in Cancer Immunology Research.

Maria Libera Ascierto, PhD, from the Johns Hopkins University School of Medicine in Baltimore, and colleagues examined mechanisms underlying the failure of PD-1-targeted therapies in patients with advanced RCC whose tumors express PD-L1. The authors derived formalin-fixed, paraffin-embedded pretreatment tumor biopsies expressing PD-L1 from 13 patients. RNA from PD-L1+ regions was subjected to whole genome microarray and multiplex quantitative real-time polymerase chain reaction gene expression analysis.

The researchers found that, following anti-PD-1 therapy, the balance between gene expression profiles reflecting metabolic pathways and immune functions correlated with clinical outcomes. In patients with PD-L1+ RCC, expression of genes involved in metabolic and solute transport functions correlated with treatment failure. Tumors from patients who responded to treatment overexpressed immune markers, including BACH2, which regulated CD4+ T cell differentiation, and CCL3, which was involved in leukocyte migration.

"These findings suggest that tumor cell-intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti-PD-1," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Bristol-Myers Squibb, which funded the study.

Source

  1. Ascierto ML, McMiller TL, Berger AE, et al. The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti-PD-1 response in Patients with Renal Cell Carcinoma. Cancer Immunol Res. 2016; doi: 10.1158.2326-6066.CIR.16-0072
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