Circulating Fatty Acid Profile as a Biomarker for Immunotherapy in Advanced Non-Small Cell Lung Cancer

• Published in: Clinical lung cancer 2022-11, Vol.23 (7), p.e489-e499
• Main Authors: Galli, Giulia, Corsetto, Paola Antonia, Proto, Claudia, Lo Russo, Giuseppe, Ganzinelli, Monica, Rulli, Eliana, Legramandi, Lorenzo, Morelli, Daniele, Ferrara, Roberto, Prelaj, Arsela, Signorelli, Diego, De Toma, Alessandro, Brambilla, Marta, Occhipinti, Mario, Manglaviti, Sara, Boeri, Mattia, Martinetti, Antonia, Vingiani, Andrea, Colombo, Mario Paolo, Rizzo, Angela Maria, Torri, Valter, de Braud, Filippo, Sangaletti, Sabina, Sica, Antonio, Garassino, Marina Chiara
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen; Biomarkers; Carcinoma, Non-Small-Cell Lung - drug therapy; Fatty acids; Fatty Acids - therapeutic use; Humans; Immunotherapy; Immunotherapy - methods; Inflammation Mediators - therapeutic use; Lipid metabolism; Lung Neoplasms - drug therapy; Membrane fluidity; Non-small cell lung cancer
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2022.07.010

•Lipid mediators influence immunity and potentially immunotherapy (IO) activity.•We investigated this topic in non-small cell lung cancer patients treated with IO.•Circulating free C16:0, esterified C16:1 and C18:0 had a positive prognostic effect.•Esterified C16:0 was negatively associated with PFS.•These fatty acids may modulate IO activity through an effect on cell membranes. Lipid metabolism impacts immune cell differentiation, activation, and functions, modulating inflammatory mediators, energy homeostasis, and cell membrane composition. Despite preclinical evidence, data in humans lack concerning tumors and immunotherapy (IO). We aimed at investigating the correlations between circulating lipids and the outcome of non-small cell lung cancer (NSCLC) patients treated with IO. We identified all patients with advanced NSCLC treated with IO at our Institution with available baseline plasma samples. Fatty acids (FAs) were analyzed through gas chromatography. Survival curves were estimated by the Kaplan-Meier method. Cox multivariate models were constructed through a stepwise procedure, with entry and exit P value set at .2. We identified 112 patients, mostly with performance status 1 (65.2%) and PD-L1≥1% (75.3%). Median progression-free survival (PFS) and overall survival (OS) were 2.8 and 11.0 months, respectively. Multivariable model for survival identified a positive association of circulating free (FFA) C16:0 (P .005) and esterified (EFA) C16:1 (P .030) with PFS, and a positive association of EFA C16:1 (P .001) and EFA C18:0 (P .020) with OS. EFA C16:0 was negatively associated with PFS (P .008). FFA C16:0 and FAs derived from its unsaturation (EFA C16:1) and elongation (EFA C18:0) are associated with a better outcome in NSCLC patients treated with IO. It is conceivable that the ratio among those FAs may modify membrane fluidity and receptor activity, influencing IO efficacy. These data pave the way for the investigation of lipid-modulating strategies in association with IO in NSCLC. We investigated the influence of baseline circulating fatty acids (FAs) on outcome upon immunotherapy in 112 advanced non-small cell lung cancer (NSCLC) patients. We identified a positive association with some esterified middle chain (C18:0) and unsaturated (C16:1) FAs, a negative association with an esterified saturated FA (C16:0). These results suggest an influence of FA metabolism on immunotherapy activity in NSCLC.