Abstract 7127: The correlation between immune status and the therapeutic efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer with sarcopenia

Abstract Background: Our previous prospective study demonstrated that non-small cell lung cancer (NSCLC) patients (pts) with pre-sarcopenia or sarcopenia exhibited poor responses to immune checkpoint inhibitors (ICIs). In this study, we evaluated the relationship between immune status and the efficacy of ICIs in NSCLC pts with sarcopenia. Method: Pts with stage IV or recurrent NSCLC receiving ICI as first-line treatment at Niigata University Medical and Dental Hospital were eligible. Sarcopenia and pre-sarcopenia were diagnosed with physical performance and skeletal muscle mass. Before ICI treatments, peripheral mononuclear blood cells (PBMCs) were collected, and immune phenotypic data was obtained by flow cytometry. Result: PBMCs were obtained from 34 pts from December 2021 through September 2024. Six patients and 7 patients were diagnosed with sarcopenia and pre-sarcopenia, respectively. Pts with a higher percentage of Lineage-CD11b+CD14+CD33+DRlow monocytic myeloid-derived suppressor cells (M-MDSCs) or Lineage-CD11b+CD15+CD33+DRlow polymorphonuclear (PMN)-MDSCs significantly shorter OS (median, 12 months (95% CI, 2.9-26.5) vs 33.1 months (95% CI, 11.4-NR); HR 2.7; P=0.035) after ICI treatments. Further, pts with PD-L1+ cells in MDSCs also had poor OS (median, 12 months (95% CI, 2.9-26.5) vs 33.1 months (95% CI, 11.4-NR); HR 2.6; P=0.0387). The higher percentage of M-MDSC (P=0.0534) and the presence of PD-L1+ cells in MDSCs (P=0.0473) tended to be associated with pts with sarcopenia or pre-sarcopenia. Conclusion: MDSCs may play a critical role in immune suppression in NSCLC pts with sarcopenia and could be associated with poor OS following ICI treatment. To improve the survival outcome of pts with sarcopenia, it is essential to establish strategies to overcome MDSC-mediated immune suppression. Citation Format: Ryo Yamazaki, Satoshi Watanabe, Takaaki Masuda, Tomoya Wakabayashi, Yumi Ando, Kunihiro Shono, Naohiro Yanagimura, Masashi Arita, Miyuki Sato, Tomohiro Tanaka, Koichiro Nozaki, Yu Saida, Kenjiro Shima, Yosuke Kimura, Nobumasa Aoki, Yasuyoshi Ohshima, Toshiyuki Koya, Toshiaki Kikuchi. The correlation between immune status and the therapeutic efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer with sarcopenia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7127.