Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden
Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/96951 |
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| author | Hyungtai Sim Hyun Jung Park Geun-Ho Park Yeon Jeong Kim Woong-Yang Park Se-Hoon Lee Murim Choi |
| author_facet | Hyungtai Sim Hyun Jung Park Geun-Ho Park Yeon Jeong Kim Woong-Yang Park Se-Hoon Lee Murim Choi |
| author_sort | Hyungtai Sim |
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| description | Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICIs), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing. Whole exome sequencing was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs. 5/42 for controls; p = 0.01). In addition, lung squamous cell carcinoma (LUSC) patients showed increased burden of larger clones compared to lung adenocarcinoma (LUAD) patients (8/43 for LUSC vs. 2/50 for LUAD; p = 0.04). Furthermore, single-cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-κB in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients. |
| format | Article |
| id | doaj-art-e3861aebdafb4a0fb0b8faf2d0801a3d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-e3861aebdafb4a0fb0b8faf2d0801a3d2024-12-20T14:26:23ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.96951Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burdenHyungtai Sim0https://orcid.org/0000-0002-3719-4190Hyun Jung Park1Geun-Ho Park2Yeon Jeong Kim3Woong-Yang Park4Se-Hoon Lee5Murim Choi6https://orcid.org/0000-0002-9195-1455Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, Republic of KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaClonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICIs), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing. Whole exome sequencing was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs. 5/42 for controls; p = 0.01). In addition, lung squamous cell carcinoma (LUSC) patients showed increased burden of larger clones compared to lung adenocarcinoma (LUAD) patients (8/43 for LUSC vs. 2/50 for LUAD; p = 0.04). Furthermore, single-cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-κB in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients.https://elifesciences.org/articles/96951clonal hematopoiesisimmune checkpoint inhibitorinflammationNSCLC |
| spellingShingle | Hyungtai Sim Hyun Jung Park Geun-Ho Park Yeon Jeong Kim Woong-Yang Park Se-Hoon Lee Murim Choi Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden eLife clonal hematopoiesis immune checkpoint inhibitor inflammation NSCLC |
| title | Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden |
| title_full | Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden |
| title_fullStr | Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden |
| title_full_unstemmed | Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden |
| title_short | Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden |
| title_sort | increased inflammatory signature in myeloid cells of non small cell lung cancer patients with high clonal hematopoiesis burden |
| topic | clonal hematopoiesis immune checkpoint inhibitor inflammation NSCLC |
| url | https://elifesciences.org/articles/96951 |
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