Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer
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 th...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.70089 |
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| author | Naoya Nishioka Tateaki Naito Takashi Sugino Koji Muramatsu Shigeki Nishihara Hiroki Urashima Nobuaki Mamesaya Haruki Kobayashi Shota Omori Ryo Ko Kazushige Wakuda Akira Ono Hirotsugu Kenmotsu Haruyasu Murakami Toshiaki Takahashi |
| author_facet | Naoya Nishioka Tateaki Naito Takashi Sugino Koji Muramatsu Shigeki Nishihara Hiroki Urashima Nobuaki Mamesaya Haruki Kobayashi Shota Omori Ryo Ko Kazushige Wakuda Akira Ono Hirotsugu Kenmotsu Haruyasu Murakami Toshiaki Takahashi |
| author_sort | Naoya Nishioka |
| collection | DOAJ |
| description | 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 < 0.05), shorter PFS (3.4 vs. 13.4 months, p < 0.05), and shorter OS (9.5 vs. 26.5 months, p < 0.05) than those with low intra‐tumoral GDF‐15 expression. Conclusion Intra‐tumoral GDF‐15 expression may predict the presence of cancer cachexia and the efficacy of PD‐1/PD‐L1 inhibitors in patients with advanced non‐small cell lung cancer. |
| format | Article |
| id | doaj-art-af78533d1f0a488b8cc82a248cf5b5e6 |
| institution | DOAJ |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj-art-af78533d1f0a488b8cc82a248cf5b5e62025-08-20T03:05:52ZengWileyThoracic Cancer1759-77061759-77142025-05-011610n/an/a10.1111/1759-7714.70089Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung CancerNaoya Nishioka0Tateaki Naito1Takashi Sugino2Koji Muramatsu3Shigeki Nishihara4Hiroki Urashima5Nobuaki Mamesaya6Haruki Kobayashi7Shota Omori8Ryo Ko9Kazushige Wakuda10Akira Ono11Hirotsugu Kenmotsu12Haruyasu Murakami13Toshiaki Takahashi14Division of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Pathology Shizuoka Cancer Center Shizuoka JapanDivision of Pathology Shizuoka Cancer Center Shizuoka JapanDepartment of CNS Research Otsuka Pharmaceutical Co., Ltd. Tokushima JapanOsaka Research Center for Drug Discovery, Department of Research Management, Otsuka Pharmaceutical Co., Ltd. Osaka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Thoracic Oncology Shizuoka Cancer Center Shizuoka JapanABSTRACT 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 < 0.05), shorter PFS (3.4 vs. 13.4 months, p < 0.05), and shorter OS (9.5 vs. 26.5 months, p < 0.05) than those with low intra‐tumoral GDF‐15 expression. Conclusion Intra‐tumoral GDF‐15 expression may predict the presence of cancer cachexia and the efficacy of PD‐1/PD‐L1 inhibitors in patients with advanced non‐small cell lung cancer.https://doi.org/10.1111/1759-7714.70089cachexiaGDF‐15non‐small cell lung cancerPD‐1/PD‐L1 inhibitorssurvival |
| spellingShingle | Naoya Nishioka Tateaki Naito Takashi Sugino Koji Muramatsu Shigeki Nishihara Hiroki Urashima Nobuaki Mamesaya Haruki Kobayashi Shota Omori Ryo Ko Kazushige Wakuda Akira Ono Hirotsugu Kenmotsu Haruyasu Murakami Toshiaki Takahashi Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer Thoracic Cancer cachexia GDF‐15 non‐small cell lung cancer PD‐1/PD‐L1 inhibitors survival |
| title | Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer |
| title_full | Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer |
| title_fullStr | Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer |
| title_full_unstemmed | Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer |
| title_short | Desensitizing Effect of Intra‐Tumoral GDF‐15 on Immunotherapy in Patients With Advanced Non‐Small Cell Lung Cancer |
| title_sort | desensitizing effect of intra tumoral gdf 15 on immunotherapy in patients with advanced non small cell lung cancer |
| topic | cachexia GDF‐15 non‐small cell lung cancer PD‐1/PD‐L1 inhibitors survival |
| url | https://doi.org/10.1111/1759-7714.70089 |
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