An immune-active tumor microenvironment favors clinical response to ipilimumab

American Cancer Society (2009) Cancer facts and figures 2009. http://www.cancer.org/acs/groups/content/@nho/documents/document/500809webpdf.pdf Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, Edwards BK (eds). SEER Cancer Statistics Review, 1975–2008, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site, 2011 Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C et al (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985, 1993. J Clin Oncol 17(7):2105–2116 Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D et al (2011) Improved survival with vemurafenib in melanoma with braf v600e mutation. N Engl J Med 364(26):2507–2516 Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723 Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok J (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526 Steer HJ, Lake RA, Nowak AK, Robinson BW (2010) Harnessing the immune response to treat cancer. Oncogene 29(48):6301–6313 Chambers CA, Kuhns MS, Egen JG, Allison JP (2001) Ctla-4-mediated inhibition in regulation of t cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 19:565–594 Murillo O, Arina A, Hervas-Stubbs S, Gupta A, McCluskey B, Dubrot J, Palazon A, Azpilikueta A, Ochoa MC, Alfaro C, Solano S et al (2008) Therapeutic antitumor efficacy of anti-cd137 agonistic monoclonal antibody in mouse models of myeloma. Clin Cancer Res 14(21):6895–6906 Chen H, Liakou CI, Kamat A, Pettaway C, Ward JF, Tang DN, Sun J, Jungbluth AA, Troncoso P, Logothetis C, Sharma P (2009) Anti-ctla-4 therapy results in higher cd4+ ICOShi t cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues. Proceedings of the National Academy of Sciences of the United States of America 106(8):2729–2734 Chambers CA, Krummel MF, Boitel B, Hurwitz A, Sullivan TJ, Fournier S, Cassell D, Brunner M, Allison JP (1996) The role of ctla-4 in the regulation and initiation of t-cell responses. Immunol Rev 153:27–46 Tarhini AA, Iqbal F (2010) CTLA-4 blockade: Therapeutic potential in cancer treatments. OncoTarg Ther 3:15–25 Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723 Harlin H, Kuna TV, Peterson AC, Meng Y, Gajewski TF (2006) Tumor progression despite massive influx of activated cd8(+) t cells in a patient with malignant melanoma ascites. Cancer Immunol Immunother 55(10):1185–1197 Kunz M, Toksoy A, Goebeler M, Engelhardt E, Brocker E, Gillitzer R (1999) Strong expression of the lymphoattractant c-x-c chemokine mig is associated with heavy infiltration of t cells in human malignant melanoma. J Pathol 189(4):552–558 Hamid O, Schmidt H, Nissan A, Ridolfi L, Aamdal S, Hansson J, Guida M, Hyams DM, Gomez H, Bastholt L, Chasalow SD, Berman D (2011) A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Trans Med 9:204 Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481 Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A et al (2008) Immunologic and clinical effects of antibody blockade of cytotoxic t lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proceedings of the National Academy of Sciences of the United States of America 105(8):3005–3010 Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG et al (1998) Interferon-inducible t cell alpha chemoattractant (i-tac): A novel non-elr cxc chemokine with potent activity on activated t cells through selective high affinity binding to cxcr3. J Exp Med 187(12):2009–2021 Liao F, Alkhatib G, Peden KW, Sharma G, Berger EA, Farber JM (1997) Strl33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and t cell line-tropic HIV-1. J Exp Med 185(11):2015–2023 Du X, Poltorak A, Wei Y, Beutler B (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11(3):362–371 Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (2004) Unc119, a novel activator of lck/fyn, is essential for t cell activation. J Exp Med 199(3):369–379 Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, Nguyen HT, Yaba P, Delicat A, Georges AJ, Russo-Marie F (1997) HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes. J Acquir Immune Defic Syndr Hum Retrovirol 16(1):1–9 Laabi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (1992) A new gene, bcm, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant t cell lymphoma. EMBO J 11(11):3897–3904 Tomlinson IM, Cook GP, Walter G, Carter NP, Riethman H, Buluwela L, Rabbitts TH, Winter G (1995) A complete map of the human immunoglobulin vh locus. Ann NY Acad Sci 764:43–46 Crouser ED, Culver DA, Knox KS, Julian MW, Shao G, Abraham S, Liyanarachchi S, Macre JE, Wewers MD, Gavrilin MA, Ross P et al (2009) Gene expression profiling identifies mmp-12 and adamdec1 as potential pathogenic mediators of pulmonary sarcoidosis. Am J Respir Crit Care Med 179(10):929–938 Bakos RM, Maier T, Besch R, Mestel DS, Ruzicka T, Sturm RA, Berking C Nestin and sox9 and sox10 transcription factors are coexpressed in melanoma. Exp Dermatol 19(8):e89–e94 Yasumoto K, Yokoyama K, Shibata K, Tomita Y, Shibahara S (1994) Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene. Mol Cell Biol 14(12):8058–8070 Hearing VJ (1973) Mammalian melanogenesis: tyrosinase versus peroxidase involvement, and activation mechanisms. Arch Biochem Biophys 158(2):720–725 Cheah MS, Wallace CD, Hoffman RM (1984) Hypomethylation of DNA in human cancer cells: a site-specific change in the c-myc oncogene. J Natl Cancer Inst 73(5):1057–1065 Rao UN, Bakker A, Swalsky PA, Finkelstein SD (1999) Max interacting protein 1: loss of heterozygosity is frequent in desmoplastic melanoma. Mod Pathol 12(4):344–350 Furlanetto RW, Harwell SE, Baggs RB (1993) Effects of insulin-like growth factor receptor inhibition on human melanomas in culture and in athymic mice. Cancer Res 53(11):2522–2526 Rieber M, Rieber MS (1994) Cyclin-dependent kinase 2 and cyclin a interaction with e2f are targets for tyrosine induction of b16 melanoma terminal differentiation. Cell Growth Differ 5(12):1339–1346 Draetta GF (1994) Mammalian g1 cyclins. Curr Opin Cell Biol 6(6):842–846 Schmollinger JC, Vonderheide RH, Hoar KM, Maecker B, Schultze JL, Hodi FS, Soiffer RJ, Jung K, Kuroda MJ, Letvin NL, Greenfield EA et al (2003) Melanoma inhibitor of apoptosis protein (ml-iap) is a target for immune-mediated tumor destruction. Proceedings of the National Academy of Sciences of the United States of America 100(6):3398–3403 Griffith TS, Chin WA, Jackson GC, Lynch DH, Kubin MZ (1998) Intracellular regulation of trail-induced apoptosis in human melanoma cells. J Immunol 161(6):2833–2840 Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ (1998) Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proceedings of the National Academy of Sciences of the United States of America 95(12):6919–6923 Parmiani G (2001) Melanoma antigens and their recognition by t cells. Keio J Med 50(2):86–90 Schoenborn JR, Wilson CB (2007) Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 96:41–101 Zeng W, Miyazato A, Chen G, Kajigaya S, Young NS, Maciejewski JP (2006) Interferon-gamma-induced gene expression in cd34 cells: Identification of pathologic cytokine-specific signature profiles. Blood 107(1):167–175 Bosco A, McKenna KL, Devitt CJ, Firth MJ, Sly PD, Holt PG (2006) Identification of novel th2-associated genes in t memory responses to allergens. J Immunol 176(8):4766–4777 Narayanan S, Silva R, Peruzzi G, Alvarez Y, Simhadri VR, Debell K, Coligan JE, Borrego F (2010) Human th1 cells that express cd300a are polyfunctional and after stimulation up-regulate the t-box transcription factor eomesodermin. PLoS One 5(5):e10636 Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, Galon J (2011) Clinical impact of different classes of infiltrating t cytotoxic and helper cells (th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71(4):1263–1271 Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF (2009) Chemokine expression in melanoma metastases associated with cd8+ t-cell recruitment. Cancer Res 69(7):3077–3085 Kalinski P, Mailliard RB, Giermasz A, Zeh HJ, Basse P, Bartlett DL, Kirkwood JM, Lotze MT, Herberman RB (2005) Natural killer-dendritic cell cross-talk in cancer immunotherapy. Expert Opin Biol Ther 5(10):1303–1315 Yuan J, Gnjatic S, Li H, Powel S, Gallardo HF, Ritter E, Ku GY, Jungbluth AA, Segal NH, Rasalan TS, Manukian G et al (2008) Ctla-4 blockade enhances polyfunctional ny-eso-1 specific t cell responses in metastatic melanoma patients with clinical benefit. Proceedings of the National Academy of Sciences of the United States of America 105(51):20410–20415 Ebrahimnejad A, Streichert T, Nollau P, Horst AK, Wagener C, Bamberger AM, Brummer J (2004) Ceacam1 enhances invasion and migration of melanocytic and melanoma cells. Am J Pathol 165(5):1781–1787 Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, Avril MF, Ortiz Romero PL, Robert T, Balacescu O, Eggermont AM et al (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98(7):472–482 Bogunovic D, O’Neill DW, Belitskaya-Levy I, Vacic V, Yu YL, Adams S, Darvishian F, Berman R, Shapiro R, Pavlick AC, Lonardi S et al (2009) Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proceedings of the National Academy of Sciences of the United States of America 106(48):20429–20434 Ascierto ML, Kmieciak M, Idowu MO, Manjili R, Zhao Y, Grimes M, Dumur C, Wang E, Ramakrishnan V, Wang XY, Bear HD et al (2011) A signature of immune function genes associated with recurrence-free survival in breast cancer patients. Breast Cancer Res Treat Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964