Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/18/4480 |
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| author | Mette T. Mouritzen Morten Ladekarl Henrik Hager Trine B. Mattesen Julie B. Lippert Malene S. Frank Anne K. Nøhr Ida B. Egendal Andreas Carus |
| author_facet | Mette T. Mouritzen Morten Ladekarl Henrik Hager Trine B. Mattesen Julie B. Lippert Malene S. Frank Anne K. Nøhr Ida B. Egendal Andreas Carus |
| author_sort | Mette T. Mouritzen |
| collection | DOAJ |
| description | Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (<i>n</i> = 25), GEP was performed using the nCounter<sup>®</sup> PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, <i>p</i> = 0.038 and OR = 0.36, <i>p</i> = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (<i>p</i> = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted <i>p</i>-values < 0.05). Conclusions: ALC above 1.01 × 10<sup>9</sup>/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC. |
| first_indexed | 2024-03-10T22:57:35Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T22:57:35Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b73130683f3147fcadf33d18a5e962c02023-11-19T09:54:24ZengMDPI AGCancers2072-66942023-09-011518448010.3390/cancers15184480Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint InhibitorsMette T. Mouritzen0Morten Ladekarl1Henrik Hager2Trine B. Mattesen3Julie B. Lippert4Malene S. Frank5Anne K. Nøhr6Ida B. Egendal7Andreas Carus8Department of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, DenmarkDepartment of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, DenmarkDepartment of Clinical Pathology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, DenmarkDepartment of Clinical Pathology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, DenmarkDepartment of Clinical Pathology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, DenmarkDepartment of Clinical Oncology and Palliative Care, Zealand University Hospital, Sygehusvej 10, 4000 Roskilde, DenmarkClinical Cancer Research Centre, Aalborg University Hospital, Sdr. Skovvej 15, 9000 Aalborg, DenmarkClinical Cancer Research Centre, Aalborg University Hospital, Sdr. Skovvej 15, 9000 Aalborg, DenmarkDepartment of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, DenmarkBackground: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (<i>n</i> = 25), GEP was performed using the nCounter<sup>®</sup> PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, <i>p</i> = 0.038 and OR = 0.36, <i>p</i> = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (<i>p</i> = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted <i>p</i>-values < 0.05). Conclusions: ALC above 1.01 × 10<sup>9</sup>/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.https://www.mdpi.com/2072-6694/15/18/4480immune checkpoint inhibitorsnon-small cell lung cancerbiomarkersgene expression analysislymphocyte countliver metastases |
| spellingShingle | Mette T. Mouritzen Morten Ladekarl Henrik Hager Trine B. Mattesen Julie B. Lippert Malene S. Frank Anne K. Nøhr Ida B. Egendal Andreas Carus Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors Cancers immune checkpoint inhibitors non-small cell lung cancer biomarkers gene expression analysis lymphocyte count liver metastases |
| title | Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors |
| title_full | Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors |
| title_fullStr | Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors |
| title_full_unstemmed | Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors |
| title_short | Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors |
| title_sort | gene expressions and high lymphocyte count may predict durable clinical benefits in patients with advanced non small cell lung cancer treated with immune checkpoint inhibitors |
| topic | immune checkpoint inhibitors non-small cell lung cancer biomarkers gene expression analysis lymphocyte count liver metastases |
| url | https://www.mdpi.com/2072-6694/15/18/4480 |
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