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Immune Response Induced in Vitro by CD16− and CD16+ Monocyte-Derived Dendritic Cells in Patients with Metastatic Renal Cell Carcinoma Treated with Dendritic Cell Vaccines

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Abstract

Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14highCD16− monocytes (16−mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16−mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-γ/IL-4 ratio against TuLy and KLH was higher when using 16−mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16−mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.

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REFERENCES

  1. Steinman RM, Pope M: Exploiting dendritic cells to improve vaccine efficacy. J Clin Invest 109: 1519-1526, 2002

    Google Scholar 

  2. Yu Z, Restifo NP: Cancer vaccines: Progress reveals new complexities. J Clin Invest 110: 289-294, 2002

    Google Scholar 

  3. Saleh MN, Goldman SJ, LoBuglio AF, Beall AC, Sabio H, McCord MC, Minasian L, Alpaugh RK, Weiner LM, Munn, DH: CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor. Blood 85: 2910-2917, 1995

    Google Scholar 

  4. Ziegler-Heitbrock HWL: Heterogeneity of human blood monocytes: The CD14+CD16+ subpopulation. Immunol Today 17: 424-428, 1996

    Google Scholar 

  5. Almeida J, Bueno C, Algueró MC, Sánchez ML, de Santiago M, Escribano L, Díaz-Agustín B, Vaquero JM, Laso FJ, San Miguel JF, Orfao A: Comparative analysis of the morphological, cytochemical, immunophenotypical, and functional characteristics of normal human peripheral blood lineage-/CD16+/HLA-DR+/CD14-/lo cells, CD14+ monocytes, and CD16- dendritic cells. Clin Immunol 100: 325-338, 2001

    Google Scholar 

  6. Randoplh GJ, Sánchez-Schmitz G, Liebman RM, Schakel K: The CD16+ (FcγRIII+ subset of human monocytes preferentially become migratory dendritic cells in a model tissue setting. J Exp Med 196: 517-527, 2002

    Google Scholar 

  7. Sanchez-Torres C, Garcia-Romo GS, Cornejo-Cortes MA, Rivas-Carvalho A, Sanchez-Schmitz G: CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. Int Immunol 13: 1571-1581, 2001

    Google Scholar 

  8. Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Mueller-Berghaus J, Kirkwood JM, Kwok WW, Storkus WJ: Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma. J Exp Med 196: 619-628, 2002

    Google Scholar 

  9. McLaughlin JK, Lipworth L: Epidemiologic aspects of renal cell cancer. Semin Oncol 27: 115-123, 2000

    Google Scholar 

  10. Motzer RJ, Russo P: Systemic therapy for renal cell carcinoma. J Urol 163: 408-417, 2000

    Google Scholar 

  11. Vogelzang NJ, Priest ER, Borden L: Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: A case with 5-year follow up. J Urol 148: 1247-1248, 1992

    Google Scholar 

  12. Schwaab T, Schned AR, Heaney JA, Cole BF, Atzpodien J, Wittke F, Ernstoff MS: In vivo description of dendritic cells in human renal cell carcinoma. J Urol 162: 567-573, 1999

    Google Scholar 

  13. Gleave ME, Elhilali M, Fradet Y, Davis I, Venner P, Saad F, Klotz LH, Moore MJ, Paton V, Bajamonde A: Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group: N Engl J Med 338: 1265-1271, 1998

    Google Scholar 

  14. Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nature Med 6: 332-336, 2000

    Google Scholar 

  15. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med 2: 52-58, 1996

    Google Scholar 

  16. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J: Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61: 6451-6458, 2001

    Google Scholar 

  17. Oosterwijk-Wakka JC, Tiemessen DM, Bleumer I, de Vries IJM, Jongmans W, Adema GJ, Debruyne FMJ, de Mulder PH, Oosterwijk E, Mulders PFA: Vaccination of patients with metastatic renal cell carcinoma with autologous dendritic cells pulsed with autologous tumor antigens in combination with interleukin-2: A phase I study. J Immunother 25: 500-508, 2002

    Google Scholar 

  18. Kondo N, Inoue R, Kasahara K, Fukao T, Kaneko H, Tashita H, Teramoto T: Reduced expression of the interferon-gamma messenger RNA in IgG2 deficiency. Scand J Immunol 45: 227-230, 1997

    Google Scholar 

  19. Ribeiro de Jesus A, Araujo I, Bacellar O, Magalhaes A, Pearce E, Harn D, Strand M, Carvalho EM: Human immune responses to Schistosoma mansoni vaccine candidate antigens. Infect Immun 68: 2797-2803, 2000

    Google Scholar 

  20. Geissman F, Jung S, Littman DR: Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19: 71-82, 2003

    Google Scholar 

  21. Soares MM, Mehta V, Finn OJ: Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. J Immunol 166: 6555-6563, 2001

    Google Scholar 

  22. Levings MK, Sangregorio R, Roncarolo MG: Human CD25+CD4+ T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 193: 1295-1302, 2001

    Google Scholar 

  23. Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR, June, CH: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol 168: 4272-4276, 2002

    Google Scholar 

  24. Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG: Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 98: 8809-8814, 2001

    Google Scholar 

  25. Finke JH, Rayman P, George R, Tannenbaum CS, Kolenko V, Uzzo R, Novick AC, Bukowski RM: Tumor-induced sensitivity to apoptosis in T cells from patients with renal cell carcinoma: Role of nuclear factor-kappaB suppression. Clin Cancer Res 7: 940s-946s, 2001

    Google Scholar 

  26. Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH, Thurnher M: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8: 3369-3376, 2002

    Google Scholar 

  27. Yi-qun Z, Joost van Neerven RJ, Kasran A, de Boer M, Ceuppens JL: Differential requirements for co-stimulatory signals from B7 family members by resting versus recently activated memory T cells towards soluble recall antigens. Int Immunol 8: 37-44, 1996

    Google Scholar 

  28. Waldrop SL, Davis KA, Maino VC, Picker LJ: Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis. J Immunol 161: 5284-5295, 1998

    Google Scholar 

  29. London CA, Lodge MP, Abbas AK: Functional responses and costimulator dependence of memory CD4+ T cells. J Immunol 164: 265-272, 2000

    Google Scholar 

  30. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin S, Kaiser LR, June CL Regulatory CD4+CD25+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61: 4766-4772, 2001

    Google Scholar 

  31. Messi M, Giacchetto I, Nagata K, Lanzavecchia A, Natoli G, Sallusto F: Memory and flexibility of cytokine gene expression as separable properties of human Th1 and Th2 lymphocytes. Nat Immunol 4: 78-86, 2003

    Google Scholar 

  32. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F: Kinetics of dendritic cell activation: Impact on priming of Th1, Th2 and nonpolarized T cells. Nat Immunol 1: 311-316, 2000

    Google Scholar 

  33. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S: Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 150: 353-360, 1993

    Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados, CINVESTAV, Av. I. P. N. 2508, Mexico City, 07360, Mexico

    J. Carlos Arroyo, Marco A. Meraz-Ríos & Carmen Sánchez-Torres

  2. Department of Urology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, INNSZ, Mexico City, Mexico

    J. Carlos Arroyo & Fernando Gabilondo

  3. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, INNSZ, Mexico City, Mexico

    Luis Llorente

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  1. J. Carlos Arroyo
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  2. Fernando Gabilondo
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  4. Marco A. Meraz-Ríos
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  5. Carmen Sánchez-Torres
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Correspondence to Carmen Sánchez-Torres.

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Arroyo, J.C., Gabilondo, F., Llorente, L. et al. Immune Response Induced in Vitro by CD16− and CD16+ Monocyte-Derived Dendritic Cells in Patients with Metastatic Renal Cell Carcinoma Treated with Dendritic Cell Vaccines. J Clin Immunol 24, 86–96 (2004). https://doi.org/10.1023/B:JOCI.0000018067.71622.fb

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  • DOI: https://doi.org/10.1023/B:JOCI.0000018067.71622.fb

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