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Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer.

Department of Chemotherapy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. karayama@hama-med.ac.jp. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. karayama@hama-med.ac.jp. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, 1231 Miyakami, Shizuoka, 424-8636, Japan. Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-ando, Shizuoka, 420-0881, Japan. Department of Respiratory Medicine, Iwata City Hospital, 513-2 Ohkubo, Iwata, 438-8550, Japan. Department of Respiratory Medicine, Shizuoka City Hospital, 10-93 Ote-cho, Shizuoka, 420-8630, Japan. Department of Respiratory Medicine, Seirei Mikatahara General Hospital, 3453 Mikatahara-cho, Hamamatsu, 433-8558, Japan. Department of Respiratory Medicine, Fujieda Municipal General Hospital, 4-1-11 Surugadai, Fujieda, 426-8677, Japan. Department of Respiratory Medicine, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, 430-8558, Japan. Department of Respiratory Medicine, Hamamatsu Rosai Hospital, 25 Shougen-cho, Hamamatsu, 430-8525, Japan. Department of Respiratory Medicine, Shizuoka Saiseikai Hospital, 1-1-1 Oshika, Shizuoka, 422-8527, Japan. Department of Respiratory Medicine, Japanese Red Cross Shizuoka Hospital, 8-2 Otemachi, Shizuoka, 420-0853, Japan. Department of Respiratory Medicine, Ensyu Hospital, 1-1-1 Chuou, Hamamatsu, 430-0929, Japan. Department of Respiratory Medicine, Hamamatsu Medical Center, 328 Tomitsuka-cho, Hamamatsu, 432-8580, Japan. Department of Respiratory Medicine, National Hospital Organization Tenryu Hospital, 4201-2 Oro, Hamamatsu, 434-8511, Japan.

Cancer immunology, immunotherapy : CII. 2022;(1):203-217
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Abstract

BACKGROUND Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

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Publication Type : Multicenter Study ; Observational Study

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