cachexia, GDF‐15, non‐small cell lung cancer, PD‐1/PD‐L1 inhibitors, survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

ABSTRACT Background Serum growth/differentiation factor 15 (GDF‐15) suppresses anti‐tumor immunity and predicts prognosis in several malignancies. Elevated GDF‐15 levels are linked to cancer cachexia, characterized by weight loss and systemic inflammation, adversely affecting patient outcomes and therapy response. However, serum GDF‐15 is not always derived from tumor tissues but also from multiple organs. Therefore, we evaluated whether intra‐tumoral GDF‐15 could be used as a biomarker for immunotherapy and its potential association with cancer cachexia. Method We retrospectively evaluated patients with advanced non‐small cell lung cancer (NSCLC) who underwent treatment with programmed cell death‐1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) inhibitors at the Shizuoka Cancer Center between 2017 and 2021. Patients with histologically confirmed NSCLC (stage III–IV or postoperative recurrence) who had undergone biopsy or surgery within 6 months prior to initiating immunotherapy were included. Expression of tumor‐derived GDF‐15 was evaluated using immunohistochemical staining of archival biopsy and surgical specimens. We analyzed the correlation between intra‐tumoral GDF‐15 expression and the incidence of cancer cachexia, as well as its impact on progression‐free survival (PFS) and overall survival (OS). Result In 6 of 35 cases, tumor cells highly expressed GDF‐15. Patients with high intra‐tumoral GDF‐15 expression had a higher incidence of cancer cachexia (100% vs. 41.4%, p