PD-L1 expression in melanoma shows marked heterogeneity within and between patients: Implications for anti-PD-1/PD-L1 clinical trials

Pigment Cell and Melanoma Research

Volumn 28, Issue 3, 2015, Pages 245-253

  Madore, Jason ^a,b   Vilain, Ricardo E ^a,b,c   Menzies, Alexander M ^a,b   Kakavand, Hojabr ^a,b   Wilmott, James S ^a,b   Hyman, Jessica ^a   Yearley, Jennifer H ^d   Kefford, Richard F ^a,b   Thompson, John F ^a,b   Long, Georgina V ^a,b   Hersey, Peter ^a,b   Scolyer, Richard A ^a,b,c  

^a MELANOMA INSTITUTE AUSTRALIA   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Biomarker; Diagnosis; Heterogeneity; Immunotherapy; Melanoma; Metastasis; Pathology; PD 1; PD L1; Prognosis

Indexed keywords

PROGRAMMED DEATH 1 LIGAND 1;

ADULT; ARTICLE; CELL COUNT; CONTROLLED STUDY; DISEASE COURSE; FEMALE; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LOCOREGIONAL METASTASIS SURVIVAL; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; MELANOMA SPECIFIC SURVIVAL; METASTASIS; METASTATIC MELANOMA; MIDDLE AGED; PRIMARY TUMOR; PROTEIN EXPRESSION; SURVIVAL; TUMOR CELL; CANCER GRADING; CLINICAL TRIAL (TOPIC); GENETIC HETEROGENEITY; IMMUNOLOGY; MELANOMA; METABOLISM; PATHOLOGY; PROGNOSIS; SKIN TUMOR; TUMOR ASSOCIATED LEUKOCYTE;

ANTIGENS, CD274; CLINICAL TRIALS AS TOPIC; FEMALE; GENETIC HETEROGENEITY; HUMANS; IMMUNOHISTOCHEMISTRY; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MELANOMA; MIDDLE AGED; NEOPLASM GRADING; NEOPLASM METASTASIS; PROGNOSIS; SKIN NEOPLASMS; SURVIVAL ANALYSIS;

EID: 84926678589     PISSN: 17551471     EISSN: 1755148X     Source Type: Journal    
DOI: 10.1111/pcmr.12340     Document Type: Article

References (25)

1. Azimi, F., Scolyer, R.A., Rumcheva, P., Moncrieff, M., Murali, R., McCarthy, S.W., Saw, R.P., and Thompson, J.F. (2012). Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J. Clin. Oncol. 30, 2678-2683.
2. Blank, C., Brown, I., Peterson, A.C., Spiotto, M., Iwai, Y., Honjo, T., and Gajewski, T.F. (2004). PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 64, 1140-1145.
3. Brahmer, J.R., Tykodi, S.S., Chow, L.Q. et al. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455-2465.
4. Budczies, J., Klauschen, F., Sinn, B.V., Gyorffy, B., Schmitt, W.D., Darb-Esfahani, S., and Denkert, C. (2012). Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One 7, e51862.
5. Daud, A.I., Hamid, O., Ribas, A. et al. (2014). Antitumor Activity of the Anti-PD1 Monoclonal Antibody MK-3475 in Melanoma (MEL): Correlation of Tumor PD-L1 Expression with Outcome. (San Diego: AACR).
6. Flies, D.B., and Chen, L. (2007). The new B7s: playing a pivotal role in tumor immunity. J. Immunother. 30, 251-260.
7. Frederick, D.T., Piris, A., Cogdill, A.P. et al. (2013). BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin. Cancer Res. 19, 1225-1231.
8. Gadiot, J., Hooijkaas, A.I., Kaiser, A.D., van Tinteren, H., van Boven, H., and Blank, C. (2011). Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer 117, 2192-2201.
9. Hamid, O., Robert, C., Daud, A. et al. (2013a). Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369, 134-144.
10. Hamid, O., Sosman, J.A., Lawrence, D.P. et al. (2013b). Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). ASCO Meet. Abstr. 31, 9010.
11. Hino, R., Kabashima, K., Kato, Y., Yagi, H., Nakamura, M., Honjo, T., Okazaki, T., and Tokura, Y. (2010). Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116, 1757-1766.
12. IBM Corp (2013). IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY: IBM Corp).
13. Keir, M.E., Liang, S.C., Guleria, I., Latchman, Y.E., Qipo, A., Albacker, L.A., Koulmanda, M., Freeman, G.J., Sayegh, M.H., and Sharpe, A.H. (2006). Tissue expression of PD-L1 mediates peripheral T cell tolerance. J. Exp. Med. 203, 883-895.
14. Lee, S.J., Jang, B.C., Lee, S.W. et al. (2006). Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 580, 755-762.
15. Murali, R., Brown, P.T., Kefford, R.F., Scolyer, R.A., Thompson, J.F., Atkins, M.B., and Long, G.V. (2012). Number of primary melanomas is an independent predictor of survival in patients with metastatic melanoma. Cancer 118, 4519-4529.
16. Pardoll, D.M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252-264.
17. Parsa, A.T., Waldron, J.S., Panner, A. et al. (2007). Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat. Med. 13, 84-88.
18. Riley, J.L. (2009). PD-1 signaling in primary T cells. Immunol. Rev. 229, 114-125.
19. Spranger, S., Spaapen, R.M., Zha, Y., Williams, J., Meng, Y., Ha, T.T., and Gajewski, T.F. (2013). Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci. Transl. Med. 5, 200ra116.
20. Taube, J.M., Anders, R.A., Young, G.D. et al. (2012). Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 4, 127ra37.
21. Taube, J.M., Klein, A.P., Brahmer, J.R., Xu, H., Pan, X., Kim, J.H., Chen, L., Pardoll, D.M., Topalian, S.L., and Anders, R.A. (2014). Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res. 20, 5064-5074.
22. Topalian, S.L., Hodi, F.S., Brahmer, J.R. et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454.
23. Topalian, S., Sznol, M., Brahmer, J. et al. (2013). Nivolumab (antiPD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: survival and long-term safety in a phase I trial. J. Clin. Oncol. 31, abstr3002.
24. Topalian, S.L., Sznol, M., McDermott, D.F. et al. (2014). Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32, 1020-1030.
25. Wolchok, J.D., Kluger, H., Callahan, M.K. et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122-133.