Molecular Pathogenesis of Hodgkin's Lymphoma: Increasing Evidence of the Importance of the Microenvironment

American Society of Clinical Oncology (ASCO) - Tập 29 Số 14 - Trang 1812-1826 - 2011
Christian Steidl1, Joseph M. Connors1, Randy D. Gascoyne1
1From the British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada.

Tóm tắt

Hodgkin's lymphoma (HL) represents the most common subtype of malignant lymphoma in young people in the Western world. Most patients can be cured with modern treatment strategies, although approximately 20% will die after relapse or progressive disease. The histologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL. HL is unique among all cancers because malignant cells are greatly outnumbered by reactive cells in the tumor microenvironment and make up only approximately 1% of the tumor. Expression of a variety of cytokines and chemokines by the HRS and LP cells is believed to be the driving force for an abnormal immune response, perpetuated by additional factors secreted by reactive cells in the microenvironment that help maintain the inflammatory milieu. The malignant HRS and LP cells manipulate the microenvironment, permitting them to develop their malignant phenotype fully and evade host immune attack. Gene expression signatures derived from non-neoplastic cells correlate well with response to initial and subsequent therapies, reflecting their functional relevance. Recent biomarker studies have added texture to clinical outcome predictors, and their incorporation into prognostic models may improve our understanding of the biologic correlates of treatment failure. Moreover, recent preclinical and clinical studies have demonstrated that the tumor microenvironment represents a promising therapeutic target, raising hope that novel treatment strategies focused on the interface between malignant and reactive cells will soon emerge.

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Tài liệu tham khảo

MJ Horner, LAG Ries, M Krapcho , etal : SEER Cancer Statistics Review, 1975-2006, National Cancer Institute http://seer.cancer.gov/csr/1975_2006/

Swerdlow SH, 2008, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

10.1136/jcp.55.3.162

10.1182/asheducation-2003.1.225

10.1056/NEJM199811193392104

10.1056/NEJMoa1000067

10.1056/NEJMe0912481

10.1182/blood-2002-01-0099

10.3109/10428190009087027

10.1016/j.exphem.2005.11.008

10.1002/(SICI)1096-9896(200002)190:2<143::AID-PATH519>3.0.CO;2-5

10.1002/hon.2900100605

10.1038/labinvest.2008.24

10.1182/blood.V85.8.2182.bloodjournal8582182

10.1016/1043-4666(90)90033-P

10.1182/blood.V93.8.2463

Kurzrock R, 1993, Cancer Res, 53, 2118

10.1084/jem.189.12.1939

10.1182/blood.V75.1.13.13

10.1615/CritRevOncog.v5.i2-3.60

10.1111/j.1365-2141.1993.tb03138.x

Merz H, 1991, Am J Pathol, 139, 1173

10.1182/blood.V78.5.1311.1311

10.1111/j.1600-0609.2005.00613.x

10.1182/blood.V87.7.2918.bloodjournal8772918

10.1016/S0002-9440(10)62238-9

10.1182/blood.V97.1.250

10.1182/blood-2006-04-015958

10.1182/blood.V98.9.2784

10.1046/j.1365-2141.2001.02977.x

10.1182/blood.V95.4.1207.004k34_1207_1213

10.1002/ijc.10399

10.1002/ijc.2910500504

Kretschmer C, 1990, Am J Pathol, 137, 341

10.1002/1097-0142(19870515)59:10<1717::AID-CNCR2820591007>3.0.CO;2-U

10.1016/0046-8177(93)90034-E

10.1080/10428190400013712

10.1016/S0002-9440(10)64878-X

10.1016/S0002-9440(10)63187-2

10.1182/blood-2007-09-112128

10.1002/path.1900

10.1016/j.leukres.2003.11.002

Hsu PL, 1991, Int J Hematol, 54, 315

10.1038/nm.2129

10.1182/blood.V88.9.3299.bloodjournal8893299

10.1002/ijc.11370

10.1182/blood.V97.6.1543

10.1182/blood.V94.6.2065

10.1016/S0002-9440(10)65424-7

10.1002/ijc.10218

10.1097/00000478-200107000-00011

10.1038/modpathol.3880473

Foss HD, 1996, Am J Pathol, 148, 1229

10.1136/mp.51.5.273

10.1093/annonc/5.suppl_1.S93

10.1093/oxfordjournals.annonc.a059218

10.1182/blood.V99.4.1109

10.1182/blood.V59.2.226.bloodjournal592226

10.3109/10428199609051610

10.3109/08830189809043013

10.1182/blood-2008-06-162404

10.1016/j.cell.2010.03.014

10.1182/blood-2004-03-0890

10.1084/jem.20030286

10.1046/j.1365-2559.2001.01083.x

10.4049/jimmunol.180.4.2284

10.1097/PAS.0b013e318165b0d6

10.1038/nrc2542

10.1182/blood.V99.4.1381

10.1182/blood.V99.4.1474

10.1002/gcc.10266

10.1182/blood-2009-12-257345

10.1182/blood-2004-09-3620

10.1182/blood-2005-09-3843

10.1038/sj.onc.1202893

10.1182/blood.V94.9.3129

10.1084/jem.191.2.395

10.1002/path.1454

10.1084/jem.20090528

10.1038/sj.onc.1209151

10.1182/blood-2007-03-082511

10.1002/ijc.1438

10.1007/BF02981951

10.1111/j.1600-065X.2008.00755.x

10.1126/science.1075762

Carbone A, 1995, Am J Pathol, 147, 912

10.1182/blood.V91.7.2443

10.1093/emboj/17.6.1700

10.1038/sj.leu.2404627

10.1182/blood.V99.2.618

10.1182/blood-2007-08-105643

10.1182/blood.V98.3.762

10.1002/path.2711

Tesch H, 1993, Am J Pathol, 142, 1714

10.1182/blood.V81.11.3097.3097

10.1182/blood.V77.11.2413.2413

10.1002/ijc.24389

10.1016/S0145-2126(98)00071-X

10.1182/blood.V97.4.1063

10.1182/blood-2004-10-4008

Willenbrock K, 2006, Haematologica, 91, 596

10.1016/j.leukres.2007.05.019

10.1097/COH.0b013e32831a722b

10.1038/nri2785

10.1182/blood-2003-07-2594

10.1182/blood-2006-04-015164

10.1002/ijc.23119

10.1189/jlb.0906565

Kadin ME, 1990, Am J Pathol, 136, 1209

Passwell J, 1983, Clin Exp Immunol, 51, 61

Cayeux SJ, 1993, Bone Marrow Transplant, 12, 603

10.1016/S1471-4906(01)02154-8

10.1158/0008-5472.CAN-05-3252

10.1080/00313020310001602567

Walker PR, 1997, J Immunol, 158, 4521, 10.4049/jimmunol.158.10.4521

10.1097/00000478-200103000-00014

10.1182/blood-2004-08-3337

10.1182/blood-2007-01-066100

10.1073/pnas.0706017104

10.1182/blood-2007-05-085159

10.1182/blood-2010-05-282780

10.1146/annurev.immunol.26.021607.090331

10.1200/JCO.2006.10.0917

10.1371/journal.pone.0010865

10.1182/asheducation-2005.1.231

10.1002/hon.804

10.1016/S0140-6736(05)66780-3

10.1073/pnas.0915054107

10.1182/blood-2007-05-086934

10.1111/j.1399-0039.2008.01005.x

10.1158/1078-0432.CCR-08-1119

10.1056/NEJMoa0905680

10.1200/JCO.2006.06.5342

10.1182/blood.V89.4.1376

10.1038/sj.leu.2402045

10.1080/10428190500220654

10.1309/NB3947K383DJ0LQ2

10.1158/1078-0432.CCR-04-1869

10.3324/haematol.11702

10.1182/blood-2008-07-168096

10.1002/1097-0142(19850715)56:2<333::AID-CNCR2820560222>3.0.CO;2-0

10.1182/blood-2005-12-5125

10.1136/jcp.53.3.182

10.1200/JCO.2005.02.6310

10.1200/JCO.2008.20.5138

10.1182/blood-2004-09-3759

10.1007/s00277-006-0081-9

10.1038/sj.onc.1205418

10.1002/1097-0142(19891015)64:8<1686::AID-CNCR2820640822>3.0.CO;2-I

10.1002/1097-0142(19940715)74:2<708::AID-CNCR2820740226>3.0.CO;2-7

10.1046/j.1365-2141.1997.d01-2010.x

10.1159/000205397

10.1002/hon.2900110404

10.1002/1097-0142(19930301)71:5<1857::AID-CNCR2820710524>3.0.CO;2-B

10.3109/10428190109097726

10.1046/j.1365-2141.2002.03768.x

10.1371/journal.pone.0006341

10.1002/1097-0142(19820501)49:9<1848::AID-CNCR2820490918>3.0.CO;2-Y

10.1182/blood-2010-02-270009

10.1182/blood-2005-04-1565

10.1002/hon.878

10.1158/0008-5472.CAN-09-1642

10.1158/1078-0432.CCR-07-1246

10.1093/ajcp/95.2.194

Delsol G, 1993, Am J Pathol, 142, 1729

10.1093/ajcp/101.6.761

10.1046/j.1365-2559.1998.t01-1-00418.x

10.1002/(SICI)1097-0215(19970207)70:4<375::AID-IJC1>3.0.CO;2-T

10.1002/(SICI)1097-0215(19970729)72:3<394::AID-IJC3>3.0.CO;2-K

Morente MM, 1997, Blood, 90, 2429

10.1038/bjc.1998.391

10.1158/0008-5472.CAN-05-0100

10.1182/blood.V77.9.1983.1983

10.1002/1097-0142(19930701)72:1<201::AID-CNCR2820720136>3.0.CO;2-V

10.3109/10428199509107894

10.1046/j.1365-2141.1998.00840.x

10.1172/JCI200316624

10.1084/jem.20080809

10.1056/NEJMoa0802885

10.3324/haematol.2009.021766

10.1182/blood-2009-06-227579

10.1002/pmic.200401286

Carvalho PC, 2007, J Exp Ther Oncol, 6, 137

10.1182/blood-2007-06-096784

10.1182/blood-2009-02-204842

10.1182/asheducation-2009.1.507

10.1002/cncr.11511

10.1002/cncr.23237

10.1182/blood-2007-03-078725

10.1182/blood.V101.2.420

10.1093/annonc/mdp277

10.1093/annonc/mdm114

10.1158/1078-0432.CCR-06-1275

10.1200/JCO.2006.07.8972

10.1158/1078-0432.CCR-09-2069

Younes A, Presented at the Annual Meeting of the American Society of Hematology

10.1111/j.1365-2141.2005.05656.x

10.1182/blood-2007-04-084756

Johnston PB, Presented at the Annual Meeting of the American Society of Hematology

10.1158/1078-0432.CCR-03-0494

10.1182/blood-2005-09-3731

10.1080/10428190701411458

Kirschbaum MH, Presented at the Annual Meeting of the American Society of Hematology

10.1182/blood-2008-01-133769

Younes A, 2009, Haematologica, 94

Fehniger TA, Presented at the Annual Meeting of the American Society of Hematology

Kuruvilla J, Presented at the Annual Meeting of the American Society of Hematology

10.1084/jem.20040890

10.1182/blood-2007-05-091280

10.1080/10428190801911704

10.1097/CJI.0b013e31815b69c8

10.1200/jco.2002.20.5.1278

10.1182/blood-2008-11-189688

10.1182/blood-2007-07-099317

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American Society of Clinical Oncology (ASCO)

Tập 29 Số 14

1812-1826

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