The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
PD-L1 expression in small cell neuroendocrine carcinomas
Open accessAbstract
Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. Aberrant PD-L1 or PD-L2 expression may cause local immune-suppression. Here we investigated expression of PD-1 and its ligands by immunohistochemistry and RNA-seq in small cell carcinomas. PD-L1 and PD-1 protein expression were analysed in 94 clinical cases of small cell carcinomas (61 pulmonary, 33 extrapulmonary) by immunohistochemistry using two different monoclonal antibodies (5H1, E1L3N). RNA expression was profiled by RNA-seq in 43 clinical cases. None of the small cell carcinomas showed PD-L1 protein expression in tumour cells. PD-L1 and PD-1 expression was noticed in the stroma: Using immunohistochemistry, 18.5% of cases (17/92) showed PD-L1 expression in tumour-infiltrating macrophages and 48% showed PD-1 positive lymphocytes (45/94). RNA-seq showed moderate PD-L1 gene expression in 37.2% (16/43). PD-L1 was correlated with macrophage and T-cell markers. The second PD-1 ligand PD-L2 was expressed in 27.9% (12/43) and showed similar correlations. Thus, the PD-1/PD-L1 pathway seems activated in a fraction of small cell carcinomas. The carcinoma cells were negative in all cases, PD-L1 was expressed in tumour-infiltrating macrophages and was correlated with tumour-infiltrating lymphocytes. Patients with stromal PD-L1/PD-L2 expression may respond to anti-PD-1 treatment. Thus, evaluation of the composition of the tumour microenvironment should be included in clinical trials. Besides conventional immunohistochemistry, RNA-seq seems suitable for detection of PD-L1/PD-L2 expression and might prove to be more sensitive.
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Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Topalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., Brahmer, J. R., Lawrence, D. P., Atkins, M. B., Powderly, J. D., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.0105 · Cited by 2,222
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Intrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity
Mahadevan, N. R., Knelson, E. H., Wolff, J. O., Vajdi, A., Saigí, M., Campisi, M., Hong, D., Thai, T. C., Piel, B., Han, S., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0913 · Cited by 227
Antonios, J. P., Soto, H., Everson, R. G., Moughon, D., Orpilla, J. R., Shin, N. P., Sedighim, S., Treger, J., Odesa, S., Tucker, A., et al. (2017) · Neuro-Oncology · doi:10.1093/neuonc/now287 · Cited by 206
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Scheel, A. H., Ansén, S., Schultheis, A. M., Scheffler, M., Fischer, R. N., Michels, S., Hellmich, M., George, J., Zander, T., Brockmann, M., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1131379 · Cited by 111
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Metadata
- Authors
- Schultheis, A. M., Scheel, A. H., Ozretić, L., George, J., Thomas, R. K., Hagemann, T., Zander, T., Wolf, J., & Buettner, R.
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 51
- Issue
- 3
- Pages
- 421-426
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2094723762
- Cited by
- 237
- References
- 4
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
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