Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker
Background Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-11-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.13650 |
| _version_ | 1819204474249412608 |
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| author | Takayo Ota Tomoya Fukui Yoshiro Nakahara Takayuki Takeda Junji Uchino Takako Mouri Keita Kudo Saki Nakajima Tomohiro Suzumura Masahiro Fukuoka |
| author_facet | Takayo Ota Tomoya Fukui Yoshiro Nakahara Takayuki Takeda Junji Uchino Takako Mouri Keita Kudo Saki Nakajima Tomohiro Suzumura Masahiro Fukuoka |
| author_sort | Takayo Ota |
| collection | DOAJ |
| description | Background Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune‐modulating factor levels for the response to anti‐PD‐1 antibodies during the first cycle in non‐small cell lung cancer (NSCLC) patients. Methods Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme‐linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. Results A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression‐free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. Conclusions Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti‐PD‐1 antibody therapy. Key points To identify a useful predictive marker for anti‐PD‐1 antibody therapy, using blood samples might be helpful. Serum baseline perforin levels were closely associated with prognosis with anti‐PD‐1 antibody therapy in non‐small cell lung cancer. |
| first_indexed | 2024-12-23T04:36:23Z |
| format | Article |
| id | doaj.art-078a03a84dfa4991824e4e520a836b94 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-12-23T04:36:23Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-078a03a84dfa4991824e4e520a836b942022-12-21T17:59:53ZengWileyThoracic Cancer1759-77061759-77142020-11-0111113223323310.1111/1759-7714.13650Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarkerTakayo Ota0Tomoya Fukui1Yoshiro Nakahara2Takayuki Takeda3Junji Uchino4Takako Mouri5Keita Kudo6Saki Nakajima7Tomohiro Suzumura8Masahiro Fukuoka9Department of Medical Oncology Izumi City General Hospital Osaka JapanDepartment of Respiratory Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Respiratory Medicine Kitasato University School of Medicine Sagamihara JapanDepartment of Respiratory Medicine Japanese Red Cross Kyoto Daini Hospital Kyoto JapanDepartment of Pulmonary Medicine Kyoto Prefectural University of Medicine Kyoto JapanDepartment of Pulmonary Medicine Kyoto Prefectural University of Medicine Kyoto JapanDepartment of Medical Oncology and Respiratory Medicine National Hospital Organization Osaka Minami Medical Center Osaka JapanDepartment of Medical Oncology and Respiratory Medicine National Hospital Organization Osaka Minami Medical Center Osaka JapanDepartment of Clinical Oncology Graduate School of Medicine, Osaka City University Osaka JapanDepartment of Medical Oncology Izumi City General Hospital Osaka JapanBackground Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune‐modulating factor levels for the response to anti‐PD‐1 antibodies during the first cycle in non‐small cell lung cancer (NSCLC) patients. Methods Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme‐linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. Results A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression‐free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. Conclusions Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti‐PD‐1 antibody therapy. Key points To identify a useful predictive marker for anti‐PD‐1 antibody therapy, using blood samples might be helpful. Serum baseline perforin levels were closely associated with prognosis with anti‐PD‐1 antibody therapy in non‐small cell lung cancer.https://doi.org/10.1111/1759-7714.13650Anti‐PD‐1 antibody therapynon‐small cell lung cancerperforinserum biomarkers |
| spellingShingle | Takayo Ota Tomoya Fukui Yoshiro Nakahara Takayuki Takeda Junji Uchino Takako Mouri Keita Kudo Saki Nakajima Tomohiro Suzumura Masahiro Fukuoka Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker Thoracic Cancer Anti‐PD‐1 antibody therapy non‐small cell lung cancer perforin serum biomarkers |
| title | Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker |
| title_full | Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker |
| title_fullStr | Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker |
| title_full_unstemmed | Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker |
| title_short | Serum immune modulators during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer: Perforin as a biomarker |
| title_sort | serum immune modulators during the first cycle of anti pd 1 antibody therapy in non small cell lung cancer perforin as a biomarker |
| topic | Anti‐PD‐1 antibody therapy non‐small cell lung cancer perforin serum biomarkers |
| url | https://doi.org/10.1111/1759-7714.13650 |
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