B cells and the humoral response in melanoma: The overlooked players of the tumor microenvironment

OncoImmunology

Volumn 6, Issue 4, 2017, Pages

  Chiaruttini, Giulia ^a   Mele, Silvia ^a   Opzoomer, James ^a   Crescioli, Silvia ^a,b   Ilieva, Kristina M ^a   Lacy, Katie E ^a   Karagiannis, Sophia N ^a,b  

^a GUY S HOSPITAL   (United Kingdom)

^b BHF Centre for Regenerative Medicine and BHF Centre of Excellence and the Biomedical Research Centre at Guy s St Thomas NHS Foundation Trust and King s College London   (United Kingdom)

Author keywords

Antibodies; B cells; humoral response; immunoglobulins; immunosurveillance; melanoma; tumor microenvironment

Indexed keywords

ALPHA2B INTERFERON; B RAF KINASE; IMMUNOGLOBULIN G4; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; RITUXIMAB; TOLL LIKE RECEPTOR AGONIST; TUMOR NECROSIS FACTOR;

ANTIGEN PRESENTATION; ANTIGEN SPECIFICITY; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; CANCER IMMUNOTHERAPY; CELL INFILTRATION; CYTOKINE PRODUCTION; CYTOKINE RELEASE; GENE REARRANGEMENT; HUMAN; HUMORAL IMMUNITY; IMMUNE DEFICIENCY; IMMUNIZATION; IMMUNOHISTOCHEMISTRY; IMMUNOLOGICAL TOLERANCE; IMMUNOSURVEILLANCE; INFLAMMATION; LYMPHANGIOGENESIS; MELANOMA; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; TERTIARY LYMPHOID STRUCTURE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT;

EID: 85017154761     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2017.1294296     Document Type: Article

References (119)

1. Schadendorf, Hauschild A. Melanoma in 2013:Melanoma-the run of success continues. Nat Rev Clin Oncol 2014; 11:75-6; PMID:24419300; http://dx.doi.org/10.1038/nrclinonc.2013.246
2. Eggermont AM, Spatz A, Robert C. Cutaneous melanoma. The Lancet 2014; 383:816-27; PMID:24054424; http://dx.doi.org/10.1016/S0140-6736(13)60802-8
3. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, et al. A landscape of driver mutations in melanoma. Cell 2012; 150:251-63; PMID:22817889; http://dx.doi.org/10.1016/j.cell.2012.06.024
4. Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 2015; 161:1681-96; PMID:26091043; http://dx.doi.org/10.1016/j.cell.2015.05.044
5. Omholt K, Karsberg S, Platz A, Kanter L, Ringborg U, Hansson J. Screening of N-ras codon 61 mutations in paired primary and metastatic cutaneous melanomas:mutations occur early and persist throughout tumor progression. Clin Cancer Res 2002; 8:3468-74; PMID:12429636
6. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417:949-54; PMID:12068308; http://dx.doi.org/10.1038/nature00766
7. Garbe C, Eigentler TK, Keilholz U, Hauschild A, Kirkwood JM. Systematic review of medical treatment in melanoma:current status and future prospects. Oncologist 2011; 16:5-24; PMID:21212434; http://dx.doi.org/10.1634/theoncologist.2010-0190
8. Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, Larkin J, Long GV, Lorigan P, McArthur GA, et al. Survival of patients with advanced metastatic melanoma:The impact of novel therapies. Eur J Cancer 2016; 53:125-34; PMID:26707829; http://dx.doi.org/10.1016/j.ejca.2015.09.013
9. Robbins HA, Clarke CA, Arron ST, Tatalovich Z, Kahn AR, Hernandez BY, Paddock L, Yanik EL, Lynch CF, Kasiske BL, et al. Melanoma risk and survival among organ transplant recipients. J Invest Dermatol 2015; 135:2657-65; PMID:26270022; http://dx.doi.org/10.1038/jid.2015.312
10. Shiels MS, Copeland G, Goodman MT, Harrell J, Lynch CF, Pawlish K, Pfeiffer RM, Engels EA. Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients. Cancer 2015; 121:2063-71; PMID:25739496; http://dx.doi.org/10.1002/cncr.29324
11. Mocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst Rev 2013; Issue 6. Art. No.:CD008955; PMID:23775773; http://dx.doi.org/10.1002/14651858.CD008955.pub2
12. Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine 2004; 28:109-23; PMID:15473953; http://dx.doi.org/10.1016/j.cyto.2004.06.010
13. Topalian SL, Gonzales MI, Parkhurst M, Li YF, Southwood S, Sette A, Rosenberg SA, Robbins PF. Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med 1996; 183:1965-71; PMID:8642306; http://dx.doi.org/10.1084/jem.183.5.1965
14. Cole DJ, Weil DP, Shamamian P, Rivoltini L, Kawakami Y, Topalian S, Jennings C, Eliyahu S, Rosenberg SA, Nishimura MI. Identification of MART-1-specific T-cell receptors:T cells utilizing distinct T-cell receptor variable and joining regions recognize the same tumor epitope. Cancer Res 1994; 54:5265-8; PMID:7522957
15. Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med 1994; 180:347-52; PMID:7516411; http://dx.doi.org/10.1084/jem.180.1.347
16. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy:moving beyond current vaccines. Nat Med 2004; 10:909-15; PMID:15340416; http://dx.doi.org/10.1038/nm1100
17. + tumor-reactive repertoire infiltrating human tumors. J Clin Invest 2014; 124:2246-59; PMID:24667641; http://dx.doi.org/10.1172/JCI73639
18. Bronte V, Kasic T, Gri G, Gallana K, Borsellino G, Marigo I, Battistini L, Iafrate M, Prayer-Galetti T, Pagano F, et al. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J Exp Med 2005; 201:1257-68; PMID:15824085; http://dx.doi.org/10.1084/jem.20042028
19. Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, Hemmi S, Hengartner H, Zinkernagel RM. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 2001; 411:1058-64; PMID:11429607; http://dx.doi.org/10.1038/35082583
20. Clemente CG, Mihm MC, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996; 77:1303-10; PMID:8608507; http://dx.doi.org/10.1002/(SICI)1097-0142(19960401)77:7%3c1303::AID-CNCR12%3e3.0.CO;2-5
21. Sim GC, Chacon J, Haymaker C, Ritthipichai K, Singh M, Hwu P, Radvanyi L. Tumor-infiltrating lymphocyte therapy for melanoma:rationale and issues for further clinical development. BioDrugs 2014; 28:421-37; PMID:24890028; http://dx.doi.org/10.1007/s40259-014-0097-y
22. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015; 348:62-8; PMID:25838374; http://dx.doi.org/10.1126/science.aaa4967
23. Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon EK, Muranski P, Restifo NP, Antony PA. Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J Exp Med 2010; 207:651-67; PMID:20156973; http://dx.doi.org/10.1084/jem.20091921
24. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711-23; PMID:20525992; http://dx.doi.org/10.1056/NEJMoa1003466
25. Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, White DE, Levy CL, Rosenberg SA, Phan GQ. CTLA-4 blockade with ipilimumab:long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012; 18:2039-47; PMID:22271879; http://dx.doi.org/10.1158/1078-0432.CCR-11-1823
26. Del Vecchio M. [AACR update on 5-year survival rates, efficacy and long-term safety in previously treated advanced/metastatic melanoma patients receiving mono-immunotherapy with nivolumab]. Recenti Prog Med 2016; 107:414-7; PMID:27571556
27. Burns MC, O'Donnell A, Puzanov I. Pembrolizumab for the treatment of advanced melanoma. Expert Opin Orphan Drugs 2016; 4:867-73; PMID:27597930; http://dx.doi.org/10.1080/21678707.2016.1191348
28. Wang W, Lau R, Yu D, Zhu W, Korman A, Weber J. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. Int Immunol 2009; 21:1065-77; PMID:19651643; http://dx.doi.org/10.1093/intimm/dxp072
29. Schildberg FA, Klein SR, Freeman GJ, Sharpe AH. Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. Immunity 2016; 44:955-72;PMID:27192563;http://dx.doi.org/10.1016/j.immuni.2016.05.002
30. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 1999; 5:1365-9; PMID:10581077; http://dx.doi.org/10.1038/70932
31. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515:568-71; PMID:25428505; http://dx.doi.org/10.1038/nature13954
32. Yamaguchi R, Tanaka M, Yano A, Tse GM, Yamaguchi M, Koura K, Kanomata N, Kawaguchi A, Akiba J, Naito Y, et al. Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer. Hum Pathol 2012; 43:1688-94; PMID:22516244; http://dx.doi.org/10.1016/j.humpath.2011.12.013
33. Woo JR, Liss MA, Muldong MT, Palazzi K, Strasner A, Ammirante M, Varki N, Shabaik A, Howell S, Kane CJ, et al. Tumor infiltrating B-cells are increased in prostate cancer tissue. J Transl Med 2014; 12:30; PMID:24475900; http://dx.doi.org/10.1186/1479-5876-12-30
34. Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH. CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 2012; 18:3281-92; PMID:22553348; http://dx.doi.org/10.1158/1078-0432.CCR-12-0234
35. Martinet L, Garrido I, Filleron T, Le Guellec S, Bellard E, Fournie JJ, Rochaix P, Girard JP. Human solid tumors contain high endothelial venules:association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res 2011; 71:5678-87; PMID:21846823; http://dx.doi.org/10.1158/0008-5472.CAN-11-0431
36. Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013; 39:782-95; PMID:24138885; http://dx.doi.org/10.1016/j.immuni.2013.10.003
37. Ladányi A, Kiss J, Mohos A, Somlai B, Liszkay G, Gilde K, Fejös Z, Gaudi I, Dobos J, Tímár J. Prognostic impact of B-cell density in cutaneous melanoma. Cancer Immunol Immunother 2011; 60:1729-38; PMID:21779876; http://dx.doi.org/10.1007/s00262-011-1071-x
38. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW, Slingluff CL. Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 2012; 72:1070-80; PMID:22266112; http://dx.doi.org/10.1158/0008-5472.CAN-11-3218
39. Garg K, Maurer M, Griss J, Brüggen MC, Wolf IH, Wagner C, Willi N, Mertz KD, Wagner SN. Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome. Hum Pathol 2016; 54:157-64; PMID:27107457; http://dx.doi.org/10.1016/j.humpath.2016.03.022
40. Hussein MR, Elsers DA, Fadel SA, Omar AE. Immunohistological characterisation of tumour infiltrating lymphocytes in melanocytic skin lesions. J Clin Pathol 2006; 59:316-24; PMID:16505286; http://dx.doi.org/10.1136/jcp.2005.028860
41. Martinez-Rodriguez M, Thompson AK, Monteagudo C. A significant percentage of CD20-positive TILs correlates with poor prognosis in patients with primary cutaneous malignant melanoma. Histopathology 2014; 65:726-8; PMID:24750176; http://dx.doi.org/10.1111/his.12437
42. Jones GW, Hill DG, Jones SA. Understanding Immune Cells in Tertiary Lymphoid Organ Development:It Is All Starting to Come Together. Front Immunol 2016; 7:401; PMID:27752256; http://dx.doi.org/10.3389/fimmu.2016.00401
43. Germain C, Gnjatic S, Dieu-Nosjean MC. Tertiary lymphoid structure-associated B cells are key players in anti-tumor immunity. Front Immunol 2015; 6:67; PMID:25755654; http://dx.doi.org/10.3389/fimmu.2015.00067
44. Siliņa K, Rulle U, Kalniņa Z, Linē A. Manipulation of tumour-infiltrating B cells and tertiary lymphoid structures:a novel anti-cancer treatment avenue? Cancer Immunol Immunother 2014; 63:643-62; PMID:24695950; http://dx.doi.org/10.1007/s00262-014-1544-9
45. Cipponi A, Mercier M, Seremet T, Baurain JF, Théate I, van den Oord J, Stas M, Boon T, Coulie PG, van Baren N. Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases. Cancer Res 2012; 72:3997-4007; PMID:22850419; http://dx.doi.org/10.1158/0008-5472.CAN-12-1377
46. Willis SN, Mallozzi SS, Rodig SJ, Cronk KM, McArdel SL, Caron T, Pinkus GS, Lovato L, Shampain KL, Anderson DE, et al. The microenvironment of germ cell tumors harbors a prominent antigen-driven humoral response. J Immunol 2009; 182:3310-7; PMID:19234230; http://dx.doi.org/10.4049/jimmunol.0803424
47. Mahmoud SM, Lee AH, Paish EC, Macmillan RD, Ellis IO, Green AR. The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat 2012; 132:545-53; PMID:21671016; http://dx.doi.org/10.1007/s10549-011-1620-1
48. Germain C, Gnjatic S, Tamzalit F, Knockaert S, Remark R, Goc J, Lepelley A, Becht E, Katsahian S, Bizouard G, et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am J Respir Crit Care Med 2014; 189:832-44; PMID:24484236; http://dx.doi.org/10.1164/rccm.201309-1611OC
49. Inoue S, Leitner WW, Golding B, Scott D. Inhibitory effects of B cells on antitumor immunity. Cancer Res 2006; 66:7741-7; PMID:16885377; http://dx.doi.org/10.1158/0008-5472.CAN-05-3766
50. Ruddell A, Harrell MI, Furuya M, Kirschbaum SB, Iritani BM. B lymphocytes promote lymphogenous metastasis of lymphoma and melanoma. Neoplasia 2011; 13:748-57; PMID:21847366; http://dx.doi.org/10.1593/neo.11756
51. Yang C, Lee H, Pal S, Jove V, Deng J, Zhang W, Hoon DS, Wakabayashi M, Forman S, Yu H. B cells promote tumor progression via STAT3 regulated-angiogenesis. PLoS One 2013; 8:e64159; PMID:23734190; http://dx.doi.org/10.1371/journal.pone.0064159
52. Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S, Korets L, Lam J, Tawfik D, DeNardo DG, et al. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 2010; 17:121-34; PMID:20138013; http://dx.doi.org/10.1016/j.ccr.2009.12.019
53. Affara NI, Ruffell B, Medler TR, Gunderson AJ, Johansson M, Bornstein S, Bergsland E, Steinhoff M, Li Y, Gong Q, et al. B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell 2014; 25:809-21; PMID:24909985; http://dx.doi.org/10.1016/j.ccr.2014.04.026
54. DiLillo DJ, Yanaba K, Tedder TF. B cells are required for optimal CD4+ and CD8+ T cell tumor immunity:therapeutic B cell depletion enhances B16 melanoma growth in mice. J Immunol 2010; 184:4006-16; PMID:20194720; http://dx.doi.org/10.4049/jimmunol.0903009
55. Kobayashi T, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K, Matsushita T. B cells promote tumor immunity against B16F10 melanoma. Am J Pathol 2014; 184:3120-9; PMID:25173132; http://dx.doi.org/10.1016/j.ajpath.2014.07.003
56. Zhou P, Qiu J, L'Italien L, Gu D, Hodges D, Chao CC, Schebye XM. Mature B cells are critical to T-cell-mediated tumor immunity induced by an agonist anti-GITR monoclonal antibody. J Immunother 2010; 33:789-97; PMID:20842058; http://dx.doi.org/10.1097/CJI.0b013e3181ee6ba9
57. Forte G, Sorrentino R, Montinaro A, Luciano A, Adcock IM, Maiolino P, Arra C, Cicala C, Pinto A, Morello S. Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma. J Immunol 2012; 189:2226-33; PMID:22826317; http://dx.doi.org/10.4049/jimmunol.1200744
58. Wennhold K, Weber TM, Thelen M, Garcia-Marquez M, Chakupurakal G, Klein-Gonzalez N, Fiedler A, Schlösser HA, Fischer R, Theurich S, et al. CD40-activated B cells induce anti-tumor immunity in vivo. Oncotarget 2016 Feb 25; PMID:26934557; http://dx.doi.org/10.18632/oncotarget.7720
59. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 2002; 16:219-30; PMID:11869683; http://dx.doi.org/10.1016/S1074-7613(02)00274-1
60. Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, et al. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011; 117:530-41; PMID:20962324; http://dx.doi.org/10.1182/blood-2010-07-294249
61. Egbuniwe I, Mohamad MH, Karagiannis SN, Nestle FO, Lacy KE. Interleukin-10-producing B-cell populations in melanoma. Br J Dermat 2012; 166, No. 4, P-21, 04.2012, p. e35
62. Ganti SN, Albershardt TC, Iritani BM, Ruddell A. Regulatory B cells preferentially accumulate in tumor-draining lymph nodes and promote tumor growth. Sci Rep 2015; 5:12255; PMID:26193241; http://dx.doi.org/10.1038/srep12255
63. Zhang Y, Gallastegui N, Rosenblatt JD. Regulatory B cells in anti-tumor immunity. Int Immunol 2015; 27:521-30; PMID:25999597; http://dx.doi.org/10.1093/intimm/dxv034
64. Shalapour S, Font-Burgada J, Di Caro G, Zhong Z, Sanchez-Lopez E, Dhar D, Willimsky G, Ammirante M, Strasner A, Hansel DE, et al. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature 2015; 521:94-8; PMID:25924065; http://dx.doi.org/10.1038/nature14395
65. + T cells to T-regulatory cells. Cancer Res 2011; 71:3505-15; PMID:21444674; http://dx.doi.org/10.1158/0008-5472.CAN-10-4316
66. Zhang Y, Eliav Y, Shin SU, Schreiber TH, Podack ER, Tadmor T, Rosenblatt JD. B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. Cancer Immunol Immunother 2013; 62:87-99; PMID:22772949; http://dx.doi.org/10.1007/s00262-012-1313-6
67. Tadmor T, Zhang Y, Cho HM, Podack ER, Rosenblatt JD. The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model. Cancer Immunol Immunother 2011; 60:609-19; PMID:21253724; http://dx.doi.org/10.1007/s00262-011-0972-z
68. Khan AR, Hams E, Floudas A, Sparwasser T, Weaver CT, Fallon PG. PD-L1hi B cells are critical regulators of humoral immunity. Nat Commun 2015; 6:5997; PMID:25609381; http://dx.doi.org/10.1038/ncomms6997
69. LeBien TW, Tedder TF. B lymphocytes:how they develop and function. Blood 2008; 112:1570-80; PMID:18725575; http://dx.doi.org/10.1182/blood-2008-02-078071
70. Chen H, Werner S, Butt J, Zörnig I, Knebel P, Michel A, Eichmüller SB, Jäger D, Waterboer T, Pawlita M, et al. Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting. Oncotarget 2016; 7:16420-32; PMID:26909861; http://dx.doi.org/10.18632/oncotarget.7500
71. Dumstrei K, Chen H, Brenner H. A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection. Oncotarget 2016; 7:11151-64; PMID:26840568
72. Katayama H, Boldt C, Ladd JJ, Johnson MM, Chao T, Capello M, Suo J, Mao J, Manson JE, Prentice R, et al. An autoimmune response signature associated with the development of triple-negative breast cancer reflects disease pathogenesis. Cancer Res 2015; 75:3246-54; PMID:26088128; http://dx.doi.org/10.1158/0008-5472.CAN-15-0248
73. Sahin U, Türeci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A 1995; 92:11810-3; PMID:8524854; http://dx.doi.org/10.1073/pnas.92.25.11810
74. Pfreundschuh M. The genealogy of SEREX. Cancer Immun 2012; 12:7; PMID:22896752
75. Gilbert AE, Karagiannis P, Dodev T, Koers A, Lacy K, Josephs DH, Takhar P, Geh JL, Healy C, Harries M, et al. Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. PLoS One 2011; 6:e19330; PMID:21559411; http://dx.doi.org/10.1371/journal.pone.0019330
76. Carpenter EL, Mick R, Rech AJ, Beatty GL, Colligon TA, Rosenfeld MR, Kaplan DE, Chang KM, Domchek SM, Kanetsky PA, et al. Collapse of the CD27+ B-cell compartment associated with systemic plasmacytosis in patients with advanced melanoma and other cancers. Clin Cancer Res 2009; 15:4277-87; PMID:19549767; http://dx.doi.org/10.1158/1078-0432.CCR-09-0537
77. Oaks M, Taylor S, Shaffer J. Autoantibodies targeting tumor-associated antigens in metastatic cancer:Sialylated IgGs as candidate anti-inflammatory antibodies. Oncoimmunology 2013; 2:e24841; PMID:23894724; http://dx.doi.org/10.4161/onci.24841
78. Saul L, Ilieva KM, Bax HJ, Karagiannis P, Correa I, Rodriguez-Hernandez I, Josephs DH, Tosi I, Egbuniwe IU, Lombardi S, et al. IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin. Sci Rep 2016; 6:29736; PMID:27411958; http://dx.doi.org/10.1038/srep29736
79. Karagiannis P, Gilbert AE, Nestle FO, Karagiannis SN. IgG4 antibodies and cancer-associated inflammation:Insights into a novel mechanism of immune escape. Oncoimmunology 2013; 2:e24889; PMID:24073371; http://dx.doi.org/10.4161/onci.24889
80. Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L, Correa I, Roberts L, Beddowes E, Koers A, et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest 2013; 123:1457-74; PMID:23454746; http://dx.doi.org/10.1172/JCI65579
81. Egbuniwe IU, Karagiannis SN, Nestle FO, Lacy KE. Revisiting the role of B cells in skin immune surveillance. Trends Immunol 2015; 36:102-11; PMID:25616715; http://dx.doi.org/10.1016/j.it.2014.12.006
82. Baumgarth N. The double life of a B-1 cell:self-reactivity selects for protective effector functions. Nat Rev Immunol 2011; 11:34-46; PMID:21151033; http://dx.doi.org/10.1038/nri2901
83. Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa M, Kodama Y, Uchida K, Okazaki K, Chiba T. Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis. Arthritis Rheum 2012; 64:914-24; PMID:21971969; http://dx.doi.org/10.1002/art.33386
84. Niwa R, Natsume A, Uehara A, Wakitani M, Iida S, Uchida K, Satoh M, Shitara K. IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides. J Immunol Methods 2005; 306:151-60; PMID:16219319; http://dx.doi.org/10.1016/j.jim.2005.08.009
85. Warncke M, Calzascia T, Coulot M, Balke N, Touil R, Kolbinger F, Heusser C. Different adaptations of IgG effector function in human and nonhuman primates and implications for therapeutic antibody treatment. J Immunol 2012; 188:4405-11; PMID:22461693; http://dx.doi.org/10.4049/jimmunol.1200090
86. Richards JO, Karki S, Lazar GA, Chen H, Dang W, Desjarlais JR. Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 2008; 7:2517-27; PMID:18723496; http://dx.doi.org/10.1158/1535-7163.MCT-08-0201
87. Seidel UJ, Schlegel P, Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Front Immunol 2013; 4:76; PMID:23543707; http://dx.doi.org/10.3389/fimmu.2013.00076
88. Labrijn AF, Buijsse AO, van den Bremer ET, Verwilligen AY, Bleeker WK, Thorpe SJ, Killestein J, Polman CH, Aalberse RC, Schuurman J, et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol 2009; 27:767-71; PMID:19620983; http://dx.doi.org/10.1038/nbt.1553
89. Davies AM, Rispens T, den Bleker TH, McDonnell JM, Gould HJ, Aalberse RC, Sutton BJ. Crystal structure of the human IgG4 C(H)3 dimer reveals the role of Arg409 in the mechanism of Fab-arm exchange. Mol Immunol 2013; 54:1-7; PMID:23164605; http://dx.doi.org/10.1016/j.molimm.2012.10.029
90. Davies AM, Rispens T, Ooijevaar-de Heer P, Gould HJ, Jefferis R, Aalberse RC, Sutton BJ. Structural determinants of unique properties of human IgG4-Fc. J Mol Biol 2014; 426:630-44; PMID:24211234; http://dx.doi.org/10.1016/j.jmb.2013.10.039
91. Crescioli S, Correa I, Karagiannis P, Davies AM, Sutton BJ, Nestle FO, Karagiannis SN. IgG4 characteristics and functions in cancer immunity. Curr Allergy Asthma Rep 2016; 16:7; PMID:26742760; http://dx.doi.org/10.1007/s11882-015-0580-7
92. Karagiannis P, Villanova F, Josephs DH, Correa I, Van Hemelrijck M, Hobbs C, Saul L, Egbuniwe IU, Tosi I, Ilieva KM, et al. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology 2015; 4:e1032492; PMID:26451312; http://dx.doi.org/10.1080/2162402X.2015.1032492
93. Aleyd E, Heineke MH, van Egmond M. The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease. Immunol Rev 2015; 268:123-38; PMID:26497517; http://dx.doi.org/10.1111/imr.12337
94. Rodríguez-Pinto D. B cells as antigen presenting cells. Cell Immunol 2005; 238:67-75; PMID:16574086; http://dx.doi.org/10.1016/j.cellimm.2006.02.005
95. Rivera A, Chen CC, Ron N, Dougherty JP, Ron Y. Role of B cells as antigen-presenting cells in vivo revisited:antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations. Int Immunol 2001; 13:1583-93; PMID:11717199; http://dx.doi.org/10.1093/intimm/13.12.1583
96. Von Bergwelt-Baildon MS, Vonderheide RH, Maecker B, Hirano N, Anderson KS, Butler MO, Xia Z, Zeng WY, Wucherpfennig KW, Nadler LM, et al. Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells:potential for clinical application. Blood 2002; 99:3319-25; PMID:11964299; http://dx.doi.org/10.1182/blood.V99.9.3319
97. Becker HJ, Kondo E, Shimabukuro-Vornhagen A, Theurich S, von Bergwelt-Baildon MS. Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells. Eur J Haematol 2016; 97:166-74; PMID:26561366; http://dx.doi.org/10.1111/ejh.12699
98. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature 1985; 314:537-9; PMID:3157869; http://dx.doi.org/10.1038/314537a0
99. Fillatreau S. Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis 2013; 72 Suppl 2:ii80-4; PMID:23253921; http://dx.doi.org/10.1136/annrheumdis-2012-202253
100. Vazquez MI, Catalan-Dibene J, Zlotnik A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine 2015; 74:318-26; PMID:25742773; http://dx.doi.org/10.1016/j.cyto.2015.02.007
101. Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines:a role in immune regulation? J Immunol 2004; 172:3422-7; PMID:15004141; http://dx.doi.org/10.4049/jimmunol.172.6.3422
102. Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, Kim HJ, Bar-Or A. Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 2007; 178:6092-9; PMID:17475834; http://dx.doi.org/10.4049/jimmunol.178.10.6092
103. Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 2000; 1:475-82; PMID:11101868; http://dx.doi.org/10.1038/82717
104. Sarwal M, Chua MS, Kambham N, Hsieh SC, Satterwhite T, Masek M, Salvatierra O. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med 2003; 349:125-38; PMID:12853585; http://dx.doi.org/10.1056/NEJMoa035588
105. Zarkhin V, Kambham N, Li L, Kwok S, Hsieh SC, Salvatierra O, Sarwal MM. Characterization of intra-graft B cells during renal allograft rejection. Kidney Int 2008; 74:664-73; PMID:18547992; http://dx.doi.org/10.1038/ki.2008.249
106. Lapointe R, Bellemare-Pelletier A, Housseau F, Thibodeau J, Hwu P. CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells. Cancer Res 2003; 63:2836-43; PMID:12782589
107. Tao H, Lu L, Xia Y, Dai F, Wang Y, Bao Y, Lundy SK, Ito F, Pan Q, Zhang X, et al. Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10. Eur J Immunol 2015; 45:999-1009; PMID:25545618; http://dx.doi.org/10.1002/eji.201444625
108. Xia Y, Tao H, Hu Y, Chen Q, Chen X, Xia L, Zhou L, Wang Y, Bao Y, Huang S, et al. IL-2 augments the therapeutic efficacy of adoptively transferred B cells which directly kill tumor cells via the CXCR4/CXCL12 and perforin pathways. Oncotarget 2016; 37:60461-74; PMID:27528023; http://dx.doi.org/10.18632/oncotarget.11124
109. Aklilu M, Stadler WM, Markiewicz M, Vogelzang NJ, Mahowald M, Johnson M, Gajewski TF. Depletion of normal B cells with rituximab as an adjunct to IL-2 therapy for renal cell carcinoma and melanoma. Ann Oncol 2004; 15:1109-14; PMID:15205206; http://dx.doi.org/10.1093/annonc/mdh280
110. Theurich S, Schlaak M, Steguweit H, Heukamp LC, Wennhold K, Kurschat P, Rabenhorst A, Hartmann K, Schlösser H, Shimabukuro-Vornhagen A, et al. Targeting tumor-infiltrating B cells in cutaneous T-cell lymphoma. J Clin Oncol 2016; 34:e110-6; PMID:25348001; http://dx.doi.org/10.1200/JCO.2013.50.9471
111. Pinc A, Somasundaram R, Wagner C, Hörmann M, Karanikas G, Jalili A, Bauer W, Brunner P, Grabmeier-Pfistershammer K, Gschaider M, et al. Targeting CD20 in melanoma patients at high risk of disease recurrence. Mol Ther 2012; 20:1056-62; PMID:22354376; http://dx.doi.org/10.1038/mt.2012.27
112. Kondo E, Gryschok L, Klein-Gonzalez N, Rademacher S, Weihrauch MR, Liebig T, Shimabukuro-Vornhagen A, Kochanek M, Draube A, von Bergwelt-Baildon MS. CD40-activated B cells can be generated in high number and purity in cancer patients:analysis of immunogenicity and homing potential. Clin Exp Immunol 2009; 155:249-56; PMID:19040609; http://dx.doi.org/10.1111/j.1365-2249.2008.03820.x
113. Coughlin CM, Vance BA, Grupp SA, Vonderheide RH. RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets:implications for pediatric immunotherapy. Blood 2004; 103:2046-54; PMID:14630810; http://dx.doi.org/10.1182/blood-2003-07-2379
114. Li Q, Lao X, Pan Q, Ning N, Yet J, Xu Y, Li S, Chang AE. Adoptive transfer of tumor reactive B cells confers host T-cell immunity and tumor regression. Clin Cancer Res 2011; 17:4987-95; PMID:21690573; http://dx.doi.org/10.1158/1078-0432.CCR-11-0207
115. Ebstein F, Keller M, Paschen A, Walden P, Seeger M, Bürger E, Krüger E, Schadendorf D, Kloetzel PM, Seifert U. Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS). Sci Rep 2016; 6:25208; PMID:27143649; http://dx.doi.org/10.1038/srep25208
116. Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 2015; 523:231-5; PMID:25970248; http://dx.doi.org/10.1038/nature14404
117. Bradley SD, Chen Z, Melendez B, Talukder A, Khalili JS, Rodriguez-Cruz T, Liu S, Whittington M, Deng W, Li F, et al. BRAFV600E co-opts a conserved MHC class I internalization pathway to diminish antigen presentation and CD8+ T-cell recognition of melanoma. Cancer Immunol Res 2015; 3:602-9; PMID:25795007; http://dx.doi.org/10.1158/2326-6066.CIR-15-0030
118. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, Roddie C, Henry JY, Yagita H, Wolchok JD, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 2013; 210:1695-710; PMID:23897981; http://dx.doi.org/10.1084/jem.20130579
119. Josephs DH, Spicer JF, Karagiannis P, Gould HJ, Karagiannis SN. IgE immunotherapy:a novel concept with promise for the treatment of cancer. MAbs 2014; 6:54-72; PMID:24423620; http://dx.doi.org/10.4161/mabs.27029