Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients

Virchows Archiv

Volumn 468, Issue 5, 2016, Pages 511-525

  Ilie, Marius ^a,b,c   Hofman, Véronique ^a,b,c   Dietel, Manfred ^d,e   Soria, Jean Charles ^f,g   Hofman, Paul ^a,b,c  

^a PASTEUR HOSPITAL   (France)

^b UNIVERSITY OF NICE SOPHIA ANTIPOLIS   (France)

^c UNIVERSITY HOSPITAL OF NICE   (France)

^d HUMBOLDT UNIVERSITY   (Germany)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f INSTITUT GUSTAVE ROUSSY   (France)

^g Universite Paris Sud   (France)

Author keywords

Diagnostic pitfalls; Immunohistochemistry; Immunotherapy; Lung cancer; PD 1; PD L1

Indexed keywords

PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 1 ANTIBODY; PROTEIN ANTIBODY; UNCLASSIFIED DRUG; PROGRAMMED DEATH 1 RECEPTOR; TUMOR MARKER;

CANCER IMMUNOTHERAPY; DIAGNOSTIC TEST; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG CANCER; NON SMALL CELL LUNG CANCER; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; ANIMAL; BIOPSY; IMMUNOTHERAPY; LUNG NEOPLASMS; METABOLISM; PATHOLOGY; PROCEDURES;

ANIMALS; BIOMARKERS, TUMOR; BIOPSY; HUMANS; IMMUNOHISTOCHEMISTRY; IMMUNOTHERAPY; LUNG NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 84964858970     PISSN: 09456317     EISSN: 14322307     Source Type: Journal    
DOI: 10.1007/s00428-016-1910-4     Document Type: Review

References (76)

1. Malvezzi M, Bertuccio P, Rosso T, Rota M, Levi F, La Vecchia C, Negri E (2015) European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol 26:779–786. doi:10.1093/annonc/mdv001
2. Scagliotti GV, Bironzo P, Vansteenkiste JF (2015) Addressing the Unmet Need in Lung Cancer: the Potential of Immuno-Oncology. Cancer Treat Rev 41:465–475. doi:10.1016/j.ctrv.2015.04.001
3. Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, Tan EH, Ho JC, Chu da T, Zaatar A, Osorio Sanchez JA, Vu VV, Au JS, Inoue A, Lee SM, Gebski V, Yang JC (2013) Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst 105:595–605. doi:10.1093/jnci/djt072
4. Shaw AT, Engelman JA (2013) ALK in lung cancer: past, present, and future. J Clin Oncol 31:1105–1111. doi:10.1200/JCO.2012.44.5353
5. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH, Eastern Cooperative Oncology G (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98. doi:10.1056/NEJMoa011954
6. Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S, Group EGW (2014) Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii27–iii39. doi:10.1093/annonc/mdu199
7. Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461. doi:10.1016/j.ccell.2015.03.001
8. Soria JC, Marabelle A, Brahmer JR, Gettinger S (2015) Immune checkpoint modulation for non-small cell lung cancer. Clin Cancer Res 21:2256–2262. doi:10.1158/1078-0432.CCR-14-2959
9. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373:123–135. doi:10.1056/NEJMoa1504627
10. Paz-Ares L, Horn L, Borghaei H, Spigel DR, Steins M, Ready N, Chow L, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaeufl M, Rodriguez O, Burgio MA, Fayette JF, Gettinger SN, Harbison C, Dorange C, Finckenstein FG, Brahmer JR (2015) Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). J Clin Oncol 33 (suppl; abstr LBA109)
11. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. doi:10.1056/NEJMoa1200690
12. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K- (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:2018–2028. doi:10.1056/NEJMoa1501824
13. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. doi:10.1056/NEJMoa1200694
14. Kerr KM, Tsao MS, Nicholson AG, Yatabe Y, Wistuba II, Hirsch FR, Committee IP (2015) Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art? J Thorac Oncol 10:985–989. doi:10.1097/JTO.0000000000000526
15. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570. doi:10.1126/science.1203486
16. Anagnostou VK, Brahmer JR (2015) Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer. Clin Cancer Res 21:976–984. doi:10.1158/1078-0432.CCR-14-1187
17. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264. doi:10.1038/nrc3239
18. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800. doi:10.1038/nm730
19. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory. T cells J Exp Med 206:3015–3029. doi:10.1084/jem.20090847
20. Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8:239–245. doi:10.1038/ni1443
21. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319. doi:10.1056/NEJMoa1411087
22. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D, Pieper RO (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13:84–88. doi:10.1038/nm1517
23. Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X, Paessler M, Wang HY, Wysocka M, Cheng M, Ruggeri BA, Wasik MA (2008) Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci U S A 105:20852–20857. doi:10.1073/pnas.0810958105
24. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127ra137. doi:10.1126/scitranslmed.3003689
25. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:563–567. doi:10.1038/nature14011
26. Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong KK (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3:1355–1363. doi:10.1158/2159-8290.CD-13-0310
27. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–571. doi:10.1038/nature13954
28. Ribas A (2015) Adaptive immune resistance: how cancer protects from immune attack. Cancer Discov 5:915–919. doi:10.1158/2159-8290.CD-15-0563
29. Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF (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. doi:10.1126/scitranslmed.3006504
30. Ibrahim R, Stewart R, Shalabi A (2015) PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol 42:474–483. doi:10.1053/j.seminoncol.2015.02.007
31. Sunshine J, Taube JM (2015) PD-1/PD-L1 inhibitors. Curr Opin Pharmacol 23:32–38. doi:10.1016/j.coph.2015.05.011
32. Jorgensen JT (2015) Companion diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC Expert Rev Mol Diagn:1–3. doi:10.1586/14737159.2016.1117389
33. Kazandjian D, Khozin S, Blumenthal G, Zhang L, Tang S, Libeg M, Kluetz P, Sridhara R, Keegan P, Pazdur R (2015) Benefit-risk summary of nivolumab for patients with metastatic squamous cell lung cancer after platinum-based chemotherapy: a report from the US Food and Drug Administration. JAMA Oncol:1–5. doi:10.1001/jamaoncol.2015.3934
34. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR, Jr., Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639. doi:10.1056/NEJMoa1507643
35. Horn L, Spigel DR, Gettinger SN, Antonia SJ, Gordon MS, Herbst RS, Sequist LV, Chappey C, Kowanetz M, Sandler A, J.C. S (2015) Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): update from a phase Ia study. J Clin Oncol 33, (suppl; abstr 8029)
36. Spira AI, Park K, Mazières J, Vansteenkiste J, Rittmeyer A, Ballinger M, Waterkamp D, Kowanetz M, He P, Fehrenbacher L (2015) Efficacy, safety and predictive biomarker results from a randomized phase II study comparing atezolizumab vs docetaxel in 2L/3L NSCLC (POPLAR). J Clin Oncol. suppl; abstr 8010
37. Spigel DR, Chaft JE, Gettinger SN, Chao BH, Dirix LY, Schmid P, Chow LQ, Chappey C, Kowanetz M, Sandler A, Funke RP, Rizvi NA (2015) Clinical activity and safety from a phase II study (FIR) of MPDL3280A (anti-PDL1) in PD-L1-selected patients with non-small cell lung cancer (NSCLC). J Clin Oncol 33, 2015 (suppl; abstr 8028)
38. Gulley JL, Spigel D, Kelly K, Chandler JC, Rajan A, Hassan R, Wong D, Leach J, Edenfield WJ, Wang D, Vrindavanam N, Weiss GJ, Gurtler JS, Grote HJ, von Heydebreck A, Chin KM, Iannotti N (2015) Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: a phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy. J Clin Oncol 33 (suppl; abstr 8034)
39. Antonia SJ, Goldberg SB, Balmanoukian AS, Sanborn RE, Steele K, Narwal R, Robbins PR, Gu Y, Karakunnel JJ, Rizvi NA (2015) Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients (pts) with advanced NSCLC J Clin Oncol 33 (suppl; abstr 3014)
40. Planchard D, Shtivelband M, Shi K, Ibrahim R, Ballas M, Soria JC (2015) A phase III study of MEDI4736 (M), an anti-PD-L1 antibody, in monotherapy or in combination with tremelimumab (T), versus standard of care (SOC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) who have received at least two prior systemic treatment regimens (ARCTIC). J Clin Oncol 33 (suppl; abstr TPS8104)
41. Chen L, Han X (2015) Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 125:3384–3391. doi:10.1172/JCI80011
42. Hansen AR, Siu LL (2015) PD-L1 testing in cancer: challenges in companion diagnostic development JAMA Oncol:1–2. doi:10.1001/jamaoncol.2015.4685
43. Bhaijee F, Anders RA (2015) PD-L1 expression as a predictive biomarker: is absence of proof the same as proof of absence?. JAMA Oncol:1–2. doi:10.1001/jamaoncol.2015.3782
44. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL (2015) Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol:1–9. doi:10.1001/jamaoncol.2015.3638
45. Ilie M, Long-Mira E, Bence C, Butori C, Lassalle S, Bouhlel L, Fazzalari L, Zahaf K, Lalvee S, Washetine K, Mouroux J, Venissac N, Poudenx M, Otto J, Sabourin JC, Marquette CH, Hofman V, Hofman P (2016) Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol 27:147–153. doi:10.1093/annonc/mdv489
46. Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Investig 94:107–116. doi:10.1038/labinvest.2013.130
47. Coghlin CL, Smith LJ, Bakar S, Stewart KN, Devereux GS, Nicolson MC, Kerr KM (2010) Quantitative analysis of tumor in bronchial biopsy specimens. J Thorac Oncol 5:448–452. doi:10.1097/JTO.0b013e3181ca12c4
48. Barsoum IB, Smallwood CA, Siemens DR, Graham CH (2014) A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res 74:665–674. doi:10.1158/0008-5472.CAN-13-0992
49. Patel SP, Kurzrock R (2015) PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 14:847–856. doi:10.1158/1535-7163.MCT-14-0983
50. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman M, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377. doi:10.1038/nature14292
51. Champiat S, Ileana E, Giaccone G, Besse B, Mountzios G, Eggermont A, Soria JC (2014) Incorporating immune-checkpoint inhibitors into systemic therapy of NSCLC. J Thorac Oncol 9:144–153. doi:10.1097/JTO.0000000000000074
52. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA (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. doi:10.1158/1078-0432.CCR-13-3271
53. Latchman YE, Liang SC, Wu Y, Chernova T, Sobel RA, Klemm M, Kuchroo VK, Freeman GJ, Sharpe AH (2004) PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci U S A 101:10691–10696. doi:10.1073/pnas.0307252101
54. Parra ER, Behrens C, Rodriguez-Canales J, Lin H, Mino B, Blando J, Lou Y, Gibbons DL, Heymach JV, Swisher SG, Weissferdt A, Kahlor N, Izzo J, Lee JJ, Kadara H, Moran C, Wistuba I (2015) High programmed cell death ligand 1 expression and low immune infiltrate score correlate with worse outcome in patients with lung adenocarcinoma Proceedings of the 106th Annual Meeting of the American Association for Cancer Research 4256
55. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D’Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pages F (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232:199–209. doi:10.1002/path.4287
56. Ascierto PA, Capone M, Urba WJ, Bifulco CB, Botti G, Lugli A, Marincola FM, Ciliberto G, Galon J, Fox BA (2013) The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment. J Transl Med 11:54. doi:10.1186/1479-5876-11-54
57. Gadiot J, Hooijkaas AI, Kaiser AD, van Tinteren H, van Boven H, Blank C (2011) Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer 117:2192–2201. doi:10.1002/cncr.25747
58. Dong H, Zhu G, Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5:1365–1369. doi:10.1038/70932
59. Sznol M, Chen L (2013) Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res 19:1021–1034. doi:10.1158/1078-0432.CCR-12-2063
60. Gatalica Z, Snyder C, Maney T, Ghazalpour A, Holterman DA, Xiao N, Overberg P, Rose I, Basu GD, Vranic S, Lynch HT, Von Hoff DD, Hamid O (2014) Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomark Prev 23:2965–2970. doi:10.1158/1055-9965.EPI-14-0654
61. Velcheti V, Rimm DL, Schalper KA (2013) Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1). J Thorac Oncol 8:803–805. doi:10.1097/JTO.0b013e318292be18
62. Schultheis AM, Scheel AH, Ozretic L, George J, Thomas RK, Hagemann T, Zander T, Wolf J, Buettner R (2015) PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer 51:421–426. doi:10.1016/j.ejca.2014.12.006
63. Komiya T, Madan R (2015) PD-L1 expression in small cell lung cancer. Eur J Cancer 51:1853–1855. doi:10.1016/j.ejca.2015.06.003
64. Boland JM, Kwon ED, Harrington SM, Wampfler JA, Tang H, Yang P, Aubry MC (2013) Tumor B7-H1 and B7-H3 expression in squamous cell carcinoma of the lung. Clin Lung Cancer 14:157–163. doi:10.1016/j.cllc.2012.05.006
65. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10:5094–5100. doi:10.1158/1078-0432.CCR-04-0428
66. Yang CY, Lin MW, Chang YL, Wu CT, Yang PC (2014) Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer 50:1361–1369. doi:10.1016/j.ejca.2014.01.018
67. Ilie M, Hofman P (2012) Pitfalls in lung cancer molecular pathology: how to limit them in routine practice? Curr Med Chem 19:2638–2651
68. Hofman V, Ilie M, Long E, Lassalle S, Butori C, Bence C, Washetine K, Lalvee S, Hofman P (2014) Immunohistochemistry and personalised medicine in lung oncology: advantages and limitations. Bull Cancer 101:958–965. doi:10.1684/bdc.2014.2041
69. Washetine K, Long E, Hofman V, Lassalle S, Ilie M, Lespinet V, Bonnetaud C, Bordone O, Gavric-Tanga V, Selva E, Reverso-Meinietti J, Sadoulet D, Lacour L, Bille Y, Lavagna R, Grier P, Zahaf K, Mari M, Hofman P (2013) The accreditation of a surgical pathology and somatic genetic laboratory (LPCE, CHU of Nice) according to the ISO 15189 norm: sharing of experience. Ann Pathol 33:386–397. doi:10.1016/j.annpat.2013.10.002
70. Long-Mira E, Washetine K, Hofman P (2015) Sense and nonsense in the process of accreditation of a pathology laboratory. Virchows Arch. doi:10.1007/s00428-015-1837-1
71. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. doi:10.1126/science.aaa1348
72. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA, Jr. (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520. doi:10.1056/NEJMoa1500596
73. Mazel M, Jacot W, Pantel K, Bartkowiak K, Topart D, Cayrefourcq L, Rossille D, Maudelonde T, Fest T, Alix-Panabieres C (2015) Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol. doi:10.1016/j.molonc.2015.05.009
74. Higgs BW, Robbins PB, Blake-Haskins JA, Zhu W, Morehouse C, Brohawn PZ, Rebelatto MC, Yao Y, Jin X, Shi L, Ranade K (2015) High tumoral IFNγ mRNA, PD-L1 protein, and combined IFNγ mRNA/PD-L1 protein expression associates with response to durvalumab (anti-PD-L1) monotherapy in NSCLC patients. Ann Oncol 26; Suppl 6, abstr 15LBA
75. Yearley J, Gibson C, Yu N, Moon C, Murphy E, McClanahan T (2015) PD-L2 expression in human tumors: relevance to anti-PD-1 therapy in cancer Ann Oncol 26; Suppl 6, abstr 18LBA
76. Ribas A, Tumeh PC (2014) The future of cancer therapy: selecting patients likely to respond to PD1/L1 blockade. Clin Cancer Res 20:4982–4984. doi:10.1158/1078-0432.CCR-14-0933