Plasma L-Arginine levels assessed by ELISA predict response of cancer patients to immune checkpoint blockers

New highlight in Annals of Oncology!

In the era of immuno-oncology, identification of reliable predictive biomarkers – that can help for a better selection of cancer patients who might respond to Immune Checkpoint Blockers (ICB) – remains crucial. Expression of PD-L1 on cancer cells, high micro satellite instability, and tumor mutational burden are, to date, the only predictors of ICB response while still being imperfect (1). Even though tumor tissue profiling is key for biomarker discovery, insights from the periphery are needed in order to allow an easy-to-implement clinical practice.

Immunometabolism is known to play a key role in shaping the immune response. Amino Acid degradation by tumor and/or suppressive immune cells has been shown to limit anti-tumor immune response (2, 3). In a recent study – supervised by Antoine Italiano and conducted in collaboration between teams from Explicyte (Bordeaux, France), Institut Bergonié (Bordeaux, France), and Institut Gustave Roussy (Villejuif, France), and published in Annals of Oncology (4)- plasmatic level of L-Arginine (Arg) has been found to be associated with clinical outcome of advanced cancer patients treated with ICB. Using an ELISA approach for Arg quantification (#IS-I-0400R) applied on two independent cohorts, Peyraud et al. demonstrated that low plasmatic level of Arg was associated with a worse clinical outcome.

As a new product on the market, our novel ELISA kit for Arg quantification (#IS-I-0400R) requires as little as 20µL plasma sample volume and therefore offers a valuable and easy approach to predicting sensitivity of patients to ICB before treatment onset.

Arg metabolism is predictive of anti-PD(L)1 immunotherapy-treated patient outcome

A. Quantification of baseline plasmatic Arg in non-durable clinical benefit (NDB ; n= 214, green) and durable clinical benefit (DCB ; n= 80, yellow) patients. p value is calculated using Wilcoxon test.

B. Kaplan Meier curves of progression-free survival according to baseline plasmatic Arg levels.

(1) Davis et al. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. October 2019
(2) Rodriguez et al. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood. February 2007
(3) Lamas et al. Altered functions of natural killer cells in response to L-Arginine availability. Cell Immunol. December 2012
(4) Peyraud et al. Circulating L-Arginine predicts survival of cancer patients treated with immune checkpoint inhibitors. Annals of Oncology. July 2022