The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Abstract
Purpose: Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas. Experimental Design: The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I–III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence. Results: On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor–negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099–0.721; P = 0.009). Conclusions: PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1–targeted therapies in breast cancer. Clin Cancer Res; 20(10); 2773–82. ©2014 AACR.
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Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
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
PD-1 and Its Ligands in Tolerance and Immunity
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Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608
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Yin–Yang of costimulation: crucial controls of immune tolerance and function
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Cited by
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733
Loss of PTEN Promotes Resistance to T Cell–Mediated Immunotherapy
Peng, W., Chen, J. Q., Liu, C., Malu, S., Creasy, C., Tetzlaff, M. T., Xu, C., McKenzie, J. A., Zhang, C., Liang, X., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0283 · Cited by 1,539
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Pathiraja, K., Aktan, G., Cheng, J. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.8931 · Cited by 1,477
Self-citationClinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890
Metadata
- Authors
- Schalper, K. A., Velcheti, V., Carvajal, D., Wimberly, H., Brown, J., Pusztai, L., & Rimm, D. L.
- Venue
- Clinical Cancer Research
- Published
- 2014-05-14
- Volume
- 20
- Issue
- 10
- Pages
- 2773-2782
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2158348986
- Cited by
- 450
- References
- 9
- FWCI
- 28.29
- Type
- journal article
- Language
- en
- Open access
- closed
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- Schalper, K. A., Velcheti, V., Carvajal, D., Wimberly, H., Brown, J., Pusztai, L., & Rimm, D. L. (2014). In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.ccr-13-2702
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