Back to Search
Start Over
Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer.
- Source :
-
Nature communications [Nat Commun] 2021 Jun 23; Vol. 12 (1), pp. 3880. Date of Electronic Publication: 2021 Jun 23. - Publication Year :
- 2021
-
Abstract
- Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC.
- Subjects :
- Antineoplastic Agents, Immunological therapeutic use
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Cell Line, Tumor
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
Neoplasm Recurrence, Local
Receptor, Notch1 metabolism
Small Cell Lung Carcinoma genetics
Small Cell Lung Carcinoma pathology
Treatment Outcome
Exome Sequencing methods
Immune Checkpoint Inhibitors therapeutic use
Lung Neoplasms drug therapy
Receptor, Notch1 genetics
Signal Transduction genetics
Small Cell Lung Carcinoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34162872
- Full Text :
- https://doi.org/10.1038/s41467-021-24164-y