Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.
Companion diagnostic devices ?Non-small cell lung cancer (NSCLC) ??The specimen should be considered to exhibit PD-L1 expression if TPS≥1% ???and high PD-L1 expression if TPS≥50% ?Gastric or gastresophageal junction (GEJ) adenocarcinoma ??The specimen should be considered to exhibit PD-L1 expression if CPS≥1 Cervical cancer ??The specimen should be considered to exhibit PD-L1 expression if CPS≥1 Urothelial carcinoma ??The specimen should be considered to exhibit PD-L1 expression if CPS≥10
P150013/S006
Companion diagnostic devices ?Non-small cell lung cancer (NSCLC) ??The specimen should be considered to exhibit PD-L1 expression if TPS≥1 ???and high PD-L1 expression if TPS≥50%
P150013/S001
Companion diagnostic devices ?Non-small cell lung cancer (NSCLC) ??The specimen should be considered PD-L1 positive if TPS≥50% of the ???viable tumor cells exhibit membrane staining at any intensity
OPDIVO® (Nivolumab)
PD-L1 28-8 pharmDx
P150027/P150027
Complementary diagnostic devices ?Non-small cell lung cancer (NSCLC) ??A minimum of 100 viable tumor cells must be present for the specimen to be ???considered adequate for PD-L1 evaluation ?Melanoma ??Specimen is considered PD-L1 positive if≥1% of melanoma cells exhibit ???circumferential and/or partial linear plasma membrane PD-L1 staining of ???tumor cells at any intensity
TECENTRIQ® (Atezolizumab)
PD-L1 (SP142)
P16002/S006
Companion diagnostic devices ?Urothelial carcinoma ??PD-L1 expression≥5% IC is indicated as an aid in identifying urothelial ???carcinoma patients ?Non-small cell lung cancer (NSCLC) ??PD-L1 expression≥50% TC or≥10% IC may be associated with enhanced ???overall survival
IMFINZI® (Durvalumab)
PD-L1 SP263
P160046
Complementary diagnostic devices ?Advanced or metastatic urothelial carcinoma ??PD-L1 status is considered high if any of the following are met: (1)≥25% of ???tumor cells exhibit membrane staining; (2) ICP>1% and IC+≥25%;(3) ICP???= 1% and IC+ = 100%
Tab.1
1
HBorghaei, L Paz-Ares, LHorn, DRSpigel, MSteins, NEReady, LQChow, EEVokes, EFelip, EHolgado, FBarlesi, MKohlhäufl, OArrieta, MABurgio, JFayette, HLena, E Poddubskaya, DEGerber, SNGettinger, CMRudin, NRizvi, LCrinò, GRBlumenschein Jr, SJAntonia, CDorange, CTHarbison, FGraf Finckenstein, JRBrahmer. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373(17): 1627–1639 https://doi.org/10.1056/NEJMoa1507643
pmid: 26412456
2
JBrahmer, KL Reckamp, PBaas, LCrinò, WEEberhardt, EPoddubskaya, SAntonia, APluzanski, EEVokes, EHolgado, DWaterhouse, NReady, JGainor, OArén Frontera, LHavel, MSteins, MCGarassino, JGAerts, MDomine, LPaz-Ares, MReck, C Baudelet, CTHarbison, BLestini, DRSpigel. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373(2): 123–135 https://doi.org/10.1056/NEJMoa1504627
pmid: 26028407
3
EBGaron, NA Rizvi, RHui, NLeighl, ASBalmanoukian, JPEder, APatnaik, CAggarwal, MGubens, LHorn, E Carcereny, MJAhn, EFelip, JSLee, MD Hellmann, OHamid, JWGoldman, JCSoria, MDolled-Filhart, RZRutledge, JZhang, JKLunceford, RRangwala, GMLubiniecki, CRoach, KEmancipator, L; KEYNOTE-001 Investigators.Gandhi Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372(21): 2018–2028 https://doi.org/10.1056/NEJMoa1501824
pmid: 25891174
4
JLarkin, V Chiarion-Sileni, RGonzalez, JJGrob, CLCowey, CDLao, D Schadendorf, RDummer, MSmylie, PRutkowski, PFFerrucci, AHill, J Wagstaff, MSCarlino, JBHaanen, MMaio, I Marquez-Rodas, GAMcArthur, PAAscierto, GVLong, MKCallahan, MAPostow, KGrossmann, MSznol, BDreno, LBastholt, AYang, LM Rollin, CHorak, FSHodi, JDWolchok. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373(1): 23–34 https://doi.org/10.1056/NEJMoa1504030
pmid: 26027431
5
CRobert, GV Long, BBrady, CDutriaux, MMaio, L Mortier, JCHassel, PRutkowski, CMcNeil, EKalinka-Warzocha, KJSavage, MMHernberg, CLebbé, JCharles, CMihalcioiu, VChiarion-Sileni, CMauch, FCognetti, AArance, HSchmidt, DSchadendorf, HGogas, LLundgren-Eriksson, CHorak, BSharkey, IMWaxman, VAtkinson, PAAscierto. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372(4): 320–330 https://doi.org/10.1056/NEJMoa1412082
pmid: 25399552
YLWTony Mok, Watson PA, Zhang J, Rangwala RA, Lopes G. Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2015; 33(15_suppl): TPS8105
8
MDHellmann, TE Ciuleanu, APluzanski, JSLee, GA Otterson, CAudigier-Valette, EMinenza, HLinardou, SBurgers, PSalman, HBorghaei, SSRamalingam, JBrahmer, MReck, KJ O’Byrne, WJGeese, GGreen, HChang, JSzustakowski, PBhagavatheeswaran, DHealey, YFu, F Nathan, LPaz-Ares. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 2018; 378(22): 2093–2104 https://doi.org/10.1056/NEJMoa1801946
pmid: 29658845
9
RJMotzer, NM Tannir, DFMcDermott, OArén Frontera, BMelichar, TKChoueiri, ERPlimack, PBarthélémy, CPorta, SGeorge, TPowles, FDonskov, VNeiman, CKKollmannsberger, PSalman, HGurney, RHawkins, ARavaud, MOGrimm, SBracarda, CHBarrios, YTomita, DCastellano, BIRini, ACChen, SMekan, MBMcHenry, MWind-Rotolo, JDoan, P Sharma, HJHammers, BEscudier; CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378(14): 1277–1290 https://doi.org/10.1056/NEJMoa1712126
pmid: 29562145
10
IMárquez-Rodas, PCerezuela, ASoria, ABerrocal, ARiso, M González-Cao, SMartín-Algarra. Immune checkpoint inhibitors: therapeutic advances in melanoma. Ann Transl Med 2015; 3(18): 267
pmid: 26605313
11
RALovell, DJ Schaeffer, SBHooser, WMHaschek, AMDahlem, WWCarmichael, VRBeasley. Toxicity of intraperitoneal doses of microcystin-LR in two strains of male mice. J Environ Pathol Toxicol Oncol 1989; 9(3): 221–237
12
DSchadendorf, FS Hodi, CRobert, JSWeber, KMargolin, OHamid, DPatt, TT Chen, DMBerman, JDWolchok. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015; 33(17): 1889–1894 https://doi.org/10.1200/JCO.2014.56.2736
pmid: 25667295
13
JSWeber, SP D’Angelo, DMinor, FSHodi, RGutzmer, BNeyns, CHoeller, NIKhushalani, WHMiller Jr, CDLao, GP Linette, LThomas, PLorigan, KFGrossmann, JCHassel, MMaio, M Sznol, PAAscierto, PMohr, B Chmielowski, ABryce, IMSvane, JJGrob, AMKrackhardt, CHorak, ALambert, ASYang, JLarkin. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015; 16(4): 375–384 https://doi.org/10.1016/S1470-2045(15)70076-8
pmid: 25795410
14
JMTaube, GD Young, TLMcMiller, TLMcMiller, SM Chen, JTSalas, TSPritchard, HY Xu, AKMeeker, JHFan, C Cheadle, AEBerger, DMPardoll, SL Topalian. Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade. Clin Cancer Res 2015; 21(17): 3969–3976
15
RSHerbst, JC Soria, MKowanetz, GDFine, OHamid, MSGordon, JASosman, DFMcDermott, JDPowderly, SNGettinger, HEKohrt, LHorn, DP Lawrence, SRost, MLeabman, YXiao, A Mokatrin, HKoeppen, PSHegde, IMellman, DSChen, FSHodi. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014; 515(7528): 563–567 https://doi.org/10.1038/nature14011
pmid: 25428504
16
JMTaube, A Klein, JRBrahmer, HYXu , XY Pan, JH Kim, LPChen, DMPardoll, SLTopalian, RA. Anders 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 2014; 20(19): 5064–5074
17
SLTopalian, FS Hodi, JRBrahmer, SNGettinger, DCSmith, DFMcDermott, JDPowderly, RDCarvajal, JASosman, MBAtkins, PDLeming, DRSpigel, SJAntonia, LHorn, CG Drake, DMPardoll, LChen, WH Sharfman, RAAnders, JMTaube, TLMcMiller, HXu, AJ Korman, MJure-Kunkel, SAgrawal, DMcDonald, GDKollia, AGupta, JMWigginton, MSznol. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443–2454 https://doi.org/10.1056/NEJMoa1200690
pmid: 22658127
18
RJMotzer, B Escudier, DFMcDermott, SGeorge, HJHammers, SSrinivas, SSTykodi, JASosman, GProcopio, ERPlimack, DCastellano, TKChoueiri, HGurney, FDonskov, PBono, J Wagstaff, TCGauler, TUeda, Y Tomita, FASchutz, CKollmannsberger, JLarkin, ARavaud, JSSimon, LAXu, IM Waxman, PSharma; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373(19): 1803–1813 https://doi.org/10.1056/NEJMoa1510665
pmid: 26406148
19
JSLim, R Sundar, MChénard-Poirier, JLopez, TAYap. Emerging biomarkers for PD-1 pathway cancer therapy. Biomarkers Med 2017; 11(1): 53–67 https://doi.org/10.2217/bmm-2016-0228
pmid: 27936870
20
JMTaube, RA Anders, GDYoung, HXu, R Sharma, TLMcMiller, SChen, AP Klein, DMPardoll, SLTopalian, LChen. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012; 4(127): 127ra37 https://doi.org/10.1126/scitranslmed.3003689
pmid: 22461641
21
ZFeng, S Puri, TMoudgil, WWood, CC Hoyt, CWang, WJUrba, BDCurti, CBBifulco, BAFox. Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma. J Immunother Cancer 2015; 3(1): 47 https://doi.org/10.1186/s40425-015-0091-z
pmid: 26500776
WYSun, YK Lee, JSKoo. Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies. J Transl Med 2016; 14(1): 173 https://doi.org/10.1186/s12967-016-0925-6
pmid: 27286842
JMarianne. AS Ratcliffe, AMidha, CBarker, PScorer, JWalker. A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16–20; New Orleans, LA. Philadelphia (PA): AACR. Cancer Res 2016; 76(14 Suppl): Abstract nr LB-094
27
DTLe, JN Uram, HWang, BRBartlett, HKemberling, ADEyring, ADSkora, BSLuber, NSAzad, DLaheru, BBiedrzycki, RCDonehower, AZaheer, GAFisher, TSCrocenzi, JJLee, SM Duffy, RMGoldberg, Ade la Chapelle, MKoshiji, FBhaijee, THuebner, RHHruban, LDWood, NCuka, DM Pardoll, NPapadopoulos, KWKinzler, SZhou, TC Cornish, JMTaube, RAAnders, JREshleman, BVogelstein, LADiaz Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372(26): 2509–2520 https://doi.org/10.1056/NEJMoa1500596
pmid: 26028255
WHugo, JM Zaretsky, LSun, CSong, BH Moreno, SHu-Lieskovan, BBerent-Maoz, JPang, B Chmielowski, GCherry, ESeja, S Lomeli, XKong, MCKelley, JASosman, DBJohnson, ARibas, RSLo. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 2016; 165(1): 35–44 https://doi.org/10.1016/j.cell.2016.02.065
pmid: 26997480
41
TFGajewski, H Schreiber, YXFu. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013; 14(10): 1014–1022 https://doi.org/10.1038/ni.2703
pmid: 24048123
42
JGalon, A Costes, FSanchez-Cabo, AKirilovsky, BMlecnik, CLagorce-Pagès, MTosolini, MCamus, ABerger, PWind, F Zinzindohoué, PBruneval, PHCugnenc, ZTrajanoski, WHFridman, FPagès. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313(5795): 1960–1964 https://doi.org/10.1126/science.1129139
pmid: 17008531
43
CJochems, J Schlom. Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity. Exp Biol Med (Maywood) 2011; 236(5): 567–579 https://doi.org/10.1258/ebm.2011.011007
pmid: 21486861
44
BMlecnik, M Tosolini, AKirilovsky, ABerger, GBindea, TMeatchi, PBruneval, ZTrajanoski, WHFridman, FPagès, JGalon. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29(6): 610–618 https://doi.org/10.1200/JCO.2010.30.5425
pmid: 21245428
45
FPagès, A Berger, MCamus, FSanchez-Cabo, ACostes, RMolidor, BMlecnik, AKirilovsky, MNilsson, DDamotte, TMeatchi, PBruneval, PHCugnenc, ZTrajanoski, WHFridman, JGalon. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353(25): 2654–2666 https://doi.org/10.1056/NEJMoa051424
pmid: 16371631
46
HMKluger, CR Zito, MLBarr, HMKluger , CRZito , MLBarr , MK Baine ,VLS Chiang , MSznol , DLRimm , LPChen , LB Jilaveanu . Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res 2015; 21(13): 3052–3060
47
LZhang, JR Conejo-Garcia, DKatsaros, PAGimotty, MMassobrio, GRegnani, AMakrigiannakis, HGray, K Schlienger, MNLiebman, SCRubin, GCoukos. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348(3): 203–213 https://doi.org/10.1056/NEJMoa020177
pmid: 12529460
48
ALadanyi, B Somlai, KGilde, ZFejos, IGaudi, JTimar. T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res 2004; 10(2): 521–530
49
KHiraoka, M Miyamoto, YCho, MSuzuoki, TOshikiri, YNakakubo, TItoh, T Ohbuchi, SKondo, HKatoh. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 2006; 94(2): 275–280 https://doi.org/10.1038/sj.bjc.6602934
pmid: 16421594
HChen, CI Liakou, AKamat, CPettaway, JFWard, DNTang, JSun, AA Jungbluth, PTroncoso, CLogothetis, PSharma. Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-γ levels in both nonmalignant and malignant prostate tissues. Proc Natl Acad Sci USA 2009; 106(8): 2729–2734 https://doi.org/10.1073/pnas.0813175106
pmid: 19202079
52
CILiakou, A Kamat, DNTang, HChen, J Sun, PTroncoso, CLogothetis, PSharma. CTLA-4 blockade increases IFNγ-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci USA 2008; 105(39): 14987–14992 https://doi.org/10.1073/pnas.0806075105
pmid: 18818309
53
RHVonderheide, PM LoRusso, MKhalil, EMGartner, DKhaira, DSoulieres, PDorazio, JATrosko, JRüter, GLMariani, TUsari, SMDomchek. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res 2010; 16(13): 3485–3494
54
DNg Tang, Y Shen, JSun, SWen, JD Wolchok, JYuan, JPAllison, PSharma. Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy. Cancer Immunol Res 2013; 1(4): 229–234 https://doi.org/10.1158/2326-6066.CIR-13-0020
pmid: 24777852
55
JWHuh, JH Lee, HRKim. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch Surg 2012; 147(4): 366–372 https://doi.org/10.1001/archsurg.2012.35
pmid: 22508783
56
NEThomas, KJ Busam, LFrom, AKricker, BKArmstrong, HAnton-Culver, SBGruber, RPGallagher, RZanetti, SRosso, TDwyer, AVenn, PA Kanetsky, PAGroben, HHao, I Orlow, ASReiner, LLuo, S Paine, DWOllila, HWilcox, CBBegg, MBerwick. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J Clin Oncol 2013; 31(33): 4252–4259 https://doi.org/10.1200/JCO.2013.51.3002
pmid: 24127443
57
DQZeng, YF Yu, QYOu, XYLi, RZ Zhong, CMXie, QGHu. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget 2016; 7(12): 13765–13781 https://doi.org/10.18632/oncotarget.7282
pmid: 26871598
58
JLMessina, DA Fenstermacher, SEschrich, XQu, AE Berglund, MCLloyd, MJSchell, VKSondak, JSWeber, JJMulé. 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep 2012; 2(1): 765 https://doi.org/10.1038/srep00765
pmid: 23097687
59
TTokito, K Azuma, AKawahara, HIshii, KYamada, NMatsuo, TKinoshita, NMizukami, HOno, M Kage, THoshino. Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Eur J Cancer 2016; 55: 7–14 https://doi.org/10.1016/j.ejca.2015.11.020
pmid: 26771872
OHamid, H Schmidt, ANissan, LRidolfi, SAamdal, JHansson, MGuida, DMHyams, HGómez, LBastholt, SDChasalow, DBerman. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 2011; 9(1): 204 https://doi.org/10.1186/1479-5876-9-204
pmid: 22123319
62
JGalon, B Mlecnik, GBindea, HKAngell, ABerger, CLagorce, ALugli, IZlobec, AHartmann, CBifulco, IDNagtegaal, RPalmqvist, GVMasucci, GBotti, FTatangelo, PDelrio, MMaio, L Laghi, FGrizzi, MAsslaber, CD’Arrigo, FVidal-Vanaclocha, EZavadova, LChouchane, PSOhashi, SHafezi-Bakhtiari, BGWouters, MRoehrl, LNguyen, YKawakami, SHazama, KOkuno, SOgino, PGibbs, PWaring, NSato, T Torigoe, KItoh, PSPatel, SNShukla, YWang, S Kopetz, FASinicrope, VScripcariu, PAAscierto, FMMarincola, BAFox, F Pagès. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 2014; 232(2): 199–209 https://doi.org/10.1002/path.4287
pmid: 24122236
63
JTsuchiya, T Maekawa. Cytokinetic studies on hematopoietic cells of the bone marrow. Nihon Ketsueki Gakkai Zasshi 1973; 36(5): 641–660
64
JGalon, BA Fox, CBBifulco, GMasucci, TRau, G Botti, FMMarincola, GCiliberto, FPages, PAAscierto, MCapone. Immunoscore and immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015. J Transl Med 2016; 14(1): 273 https://doi.org/10.1186/s12967-016-1029-z
pmid: 27650038
65
FPagès, A Kirilovsky, BMlecnik, MAsslaber, MTosolini, GBindea, CLagorce, PWind, F Marliot, PBruneval, KZatloukal, ZTrajanoski, ABerger, WHFridman, JGalon. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 2009; 27(35): 5944–5951 https://doi.org/10.1200/JCO.2008.19.6147
pmid: 19858404
PAAscierto, M Capone, WJUrba, CBBifulco, GBotti, ALugli, FMMarincola, GCiliberto, JGalon, BAFox. The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment. J Transl Med 2013; 11(1): 54 https://doi.org/10.1186/1479-5876-11-54
pmid: 23452415
68
EEPaulsen , TK Kilvaer , MRKhanehkenari, SAl-Saad, SM Hald , SAndersen, ERichardsen, NNess, LTBusund , RMBremnes , TDonnem. Assessing PDL-1 and PD-1 in non-small cell lung cancer: a novel immunoscore approach. Clin Lung Cancer 2017; 18(2): 220–333.e8 https://doi.org/10.1016/j.cllc.2016.09.009
69
JYuan, J Zhou, ZDong, STandon, DKuk, KS Panageas, PWong, XWu, J Naidoo, DBPage, JDWolchok, FSHodi. Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res 2014; 2(2): 127–132 https://doi.org/10.1158/2326-6066.CIR-13-0163
pmid: 24778276
70
SKelderman, B Heemskerk, Hvan Tinteren, RRvan den Brom, GAHospers, AJvan den Eertwegh, EWKapiteijn, JWde Groot, PSoetekouw, RLJansen, EFiets, AJFurness, ARenn, M Krzystanek, ZSzallasi, PLorigan, MEGore, TNSchumacher, JBHaanen, JMLarkin, CUBlank. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 2014; 63(5): 449–458 https://doi.org/10.1007/s00262-014-1528-9
pmid: 24609989
71
ESimeone, G Gentilcore, DGiannarelli, AMGrimaldi, CCaracò, MCurvietto, AEsposito, MPaone, MPalla, ECavalcanti, FSandomenico, APetrillo, GBotti, FFulciniti, GPalmieri, PQueirolo, PMarchetti, VFerraresi, GRinaldi, MPPistillo, GCiliberto, NMozzillo, PAAscierto. Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. Cancer Immunol Immunother 2014; 63(7): 675–683 https://doi.org/10.1007/s00262-014-1545-8
pmid: 24695951
72
DHannani, M Vétizou, DEnot, SRusakiewicz, NChaput, DKlatzmann, MDesbois, NJacquelot, NVimond, SChouaib, CMateus, JPAllison, ARibas, JDWolchok, JYuan, P Wong, MPostow, AMackiewicz, JMackiewicz, DSchadendorff, DJaeger, IZörnig, JHassel, AJKorman, KBahjat, MMaio, L Calabro, MWTeng, MJSmyth, AEggermont, CRobert, GKroemer, LZitvogel. Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25. Cell Res 2015; 25(2): 208–224 https://doi.org/10.1038/cr.2015.3
pmid: 25582080
73
JDelyon, C Mateus, DLefeuvre, ELanoy, LZitvogel, NChaput, SRoy, AM Eggermont, ERoutier, CRobert. Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. Ann Oncol 2013; 24(6): 1697–1703 https://doi.org/10.1093/annonc/mdt027
pmid: 23439861
74
AMartens, K Wistuba-Hamprecht, MGeukes Foppen, JYuan, MAPostow , PWong, E,Romano AKhammari, BDreno, MCapone, PA Ascierto , AMDi Giacomo , MMaio, B Schilling, ASucker, DSchadendorf, JC Hassel , TKEigentler, PMartus, JD Wolchok, CBlank, GPawelec, CGarbe, BWeide. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res 2016; 22(12): 2908–2918 https://doi.org/10.1158/1078-0432.CCR-15-2412
75
HSchmidt, S Suciu, CJPunt, MGore, W Kruit, PPatel, DLienard, Hvon der Maase, AMEggermont, UKeilholz; American Joint Committee on Cancer Stage IV Melanoma; EORTC 18951. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol 2007; 25(12): 1562–1569 https://doi.org/10.1200/JCO.2006.09.0274
pmid: 17443000
76
CMeyer, L Cagnon, CMCosta-Nunes, PBaumgaertner, NMontandon, LLeyvraz, OMichielin, ERomano, DESpeiser. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 2014; 63(3): 247–257 https://doi.org/10.1007/s00262-013-1508-5
pmid: 24357148
77
JYuan, M Adamow, BAGinsberg, TSRasalan, ERitter, HFGallardo, YXu, E Pogoriler, SLTerzulli, DKuk, KS Panageas, GRitter, MSznol, RHalaban, AAJungbluth, JPAllison, LJOld, JD Wolchok, SGnjatic. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci USA 2011; 108(40): 16723–16728 https://doi.org/10.1073/pnas.1110814108
pmid: 21933959