دورية أكاديمية
Beyond Programmed Death-Ligand 1: B7-H6 Emerges as a Potential Immunotherapy Target in SCLC.
| العنوان: | Beyond Programmed Death-Ligand 1: B7-H6 Emerges as a Potential Immunotherapy Target in SCLC. |
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| المؤلفون: | Thomas PL; Department of Microbiology, Immunology & Physiology, School of Medicine, Meharry Medical College, Nashville, Tennessee; School of Graduate Studies & Research, Meharry Medical College, Nashville, Tennessee., Groves SM; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee., Zhang YK; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Li J; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Gonzalez-Ericsson P; Breast Cancer Research Program, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee., Sivagnanam S; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon., Betts CB; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon., Chen HC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Liu Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Lowe C; Department of Pathology, Immunology and Microbiology, Vanderbilt University Medical Center, Nashville, Tennessee., Chen H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Boyd KL; Department of Pathology, Immunology and Microbiology, Vanderbilt University Medical Center, Nashville, Tennessee., Kopparapu PR; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Yan Y; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Coussens LM; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon., Quaranta V; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee., Tyson DR; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee., Iams W; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Lovly CM; School of Graduate Studies & Research, Meharry Medical College, Nashville, Tennessee; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: christine.lovly@vumc.org. |
| المصدر: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2021 Jul; Vol. 16 (7), pp. 1211-1223. Date of Electronic Publication: 2021 Apr 08. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101274235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-1380 (Electronic) Linking ISSN: 15560864 NLM ISO Abbreviation: J Thorac Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York, NY : Elsevier Original Publication: Hagerstown, MD : Lippincott Williams & Wilkins, c2006- |
| مواضيع طبية MeSH: | Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Small Cell Lung Carcinoma*/drug therapy , Small Cell Lung Carcinoma*/genetics, B7-H1 Antigen ; Humans ; Immunotherapy ; Progression-Free Survival |
| مستخلص: | Introduction: The programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, atezolizumab and durvalumab, have received regulatory approval for the first-line treatment of patients with extensive-stage SCLC. Nevertheless, when used in combination with platinum-based chemotherapy, these PD-L1 inhibitors only improve overall survival by 2 to 3 months. This may be due to the observation that less than 20% of SCLC tumors express PD-L1 at greater than 1%. Evaluating the composition and abundance of checkpoint molecules in SCLC may identify molecules beyond PD-L1 that are amenable to therapeutic targeting. Methods: We analyzed RNA-sequencing data from SCLC cell lines (n = 108) and primary tumor specimens (n = 81) for expression of 39 functionally validated inhibitory checkpoint ligands. Furthermore, we generated tissue microarrays containing SCLC cell lines and patient with SCLC specimens to confirm expression of these molecules by immunohistochemistry. We annotated patient outcomes data, including treatment response and overall survival. Results: The checkpoint protein B7-H6 (NCR3LG1) exhibited increased protein expression relative to PD-L1 in cell lines and tumors (p < 0.05). Higher B7-H6 protein expression correlated with longer progression-free survival (p = 0.0368) and increased total immune infiltrates (CD45+) in patients. Furthermore, increased B7-H6 gene expression in SCLC tumors correlated with a decreased activated natural killer cell gene signature, suggesting a complex interplay between B7-H6 expression and immune signature in SCLC. Conclusions: We investigated 39 inhibitory checkpoint molecules in SCLC and found that B7-H6 is highly expressed and associated with progression-free survival. In addition, 26 of 39 immune checkpoint proteins in SCLC tumors were more abundantly expressed than PD-L1, indicating an urgent need to investigate additional checkpoint targets for therapy in addition to PD-L1. (Published by Elsevier Inc.) |
| التعليقات: | Comment in: J Thorac Oncol. 2021 Jul;16(7):1056-1057. (PMID: 34154789) |
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| معلومات مُعتمدة: | U54 CA217450 United States CA NCI NIH HHS; S10 OD023475 United States OD NIH HHS; S10 OD016355 United States OD NIH HHS; K12 CA090625 United States CA NCI NIH HHS; R01 CA223150 United States CA NCI NIH HHS; S21 MD000104 United States MD NIMHD NIH HHS; R50 CA243783 United States CA NCI NIH HHS; P30 CA068485 United States CA NCI NIH HHS; R01 CA226909 United States CA NCI NIH HHS; UL1 TR000445 United States TR NCATS NIH HHS; R21 HD099367 United States HD NICHD NIH HHS; U01 CA224276 United States CA NCI NIH HHS; U01 CA224012 United States CA NCI NIH HHS; U2C CA233280 United States CA NCI NIH HHS; UG1 CA233259 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: B7-H6; Checkpoint molecules; Immune checkpoint inhibitor; Immunotherapy; Small cell lung cancer (SCLC) |
| المشرفين على المادة: | 0 (B7-H1 Antigen) |
| تواريخ الأحداث: | Date Created: 20210411 Date Completed: 20210809 Latest Revision: 20220719 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8222171 |
| DOI: | 10.1016/j.jtho.2021.03.011 |
| PMID: | 33839362 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1556-1380 |
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| DOI: | 10.1016/j.jtho.2021.03.011 |