Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Does chemotherapy modify the immune surveillance of hematological malignancies?

Leukemia volume 23, pages 53–58 (2009)Cite this article

Abstract

Malignant diseases induce immune responses against them which have variable success in controlling progression of disease. A variety of congenital and acquired disorders provide evidence in support of T cell or NK cell immune surveillance mechanisms in human hematological malignancies. Furthermore, clinical experience with stem cell transplantation underlines the potential for both T and NK cell-mediated antileukemia effects. Animal models of tumor surveillance and viral-driven lymphoproliferative diseases in man emphasize the dynamic nature of the equilibrium between tumors and the immune system, which can lead to tumor escape in individuals with normal immune function. In hematological malignancies the implication of a dynamic immune surveillance model is that chemotherapy may disrupt potentially competent immune surveillance mechanisms leading to disease recurrence following successful tumor bulk reduction by chemotherapy. This possibility deserves further investigation with a view to developing strategies to boost immune function following chemotherapy so as to combine the beneficial effect of chemotherapy with an immune response capable of sustaining remissions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Ehrlich P . Ueber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd 1909; 5: 273–290.

    Google Scholar 

  2. Thomas L . Reactions to homologous tissue antigens in relation to hypersensitivity (discussion). In: Lawrence HS (ed). Cellullar and Humoral Aspects of the Hyperseisitive States. Hoeber-Harper: New York, NY, USA, 1959, pp 529–532.

    Google Scholar 

  3. Burnet FM . The concept of immunological surveillance. Prog Exp Tumor Res 1970; 13: 1–27.

    Article  CAS  Google Scholar 

  4. Dunn GP, Old LJ, Schreiber RD . The three Es of cancer immunoediting. Annu Rev Immunol 2004; 22: 329–360.

    Article  CAS  Google Scholar 

  5. Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS . Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency 1994; 5: 91–112.

    CAS  PubMed  Google Scholar 

  6. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313: 1960–1964.

    Article  CAS  Google Scholar 

  7. Swann JB, Smyth MJ . Immune surveillance of tumors. J Clin Invest 2007; 117: 1137–1146.

    Article  CAS  Google Scholar 

  8. Street SE, Hayakawa Y, Zhan Y, Lew AM, MacGregor D, Jamieson AM et al. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med 2004; 199: 879–884.

    Article  CAS  Google Scholar 

  9. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K . Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 2000; 356: 1795–1799.

    Article  CAS  Google Scholar 

  10. Smyth MJ, Dunn GP, Schreiber RD . Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 2006; 90: 1–50.

    Article  CAS  Google Scholar 

  11. Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007; 450: 903–907.

    Article  CAS  Google Scholar 

  12. Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA . Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 2002; 100: 1935–1947.

    Article  CAS  Google Scholar 

  13. Palmer S, Hanson CA, Zent CS, Porrata LF, Laplant B, Geyer SM et al. Prognostic importance of T and NK-cells in a consecutive series of newly diagnosed patients with chronic lymphocytic leukaemia. Br J Haematol 2008; 141: 607–614.

    Article  Google Scholar 

  14. Lowdell MW, Craston R, Samuel D, Wood ME, O'Neill E, Saha V et al. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells. Br J Haematol 2002; 117: 821–827.

    Article  CAS  Google Scholar 

  15. Dolcetti R . B lymphocytes and Epstein-Barr virus: the lesson of post-transplant lymphoproliferative disorders. Autoimmun Rev 2007; 7: 96–101.

    Article  CAS  Google Scholar 

  16. Gottschalk S, Heslop HE, Rooney CM . Adoptive immunotherapy for EBV-associated malignancies. Leuk Lymphoma 2005; 46: 1–10.

    Article  CAS  Google Scholar 

  17. Gottschalk S, Ng CY, Perez M, Smith CA, Sample C, Brenner MK et al. An Epstein-Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsive to therapy with virus-specific CTLs. Blood 2001; 97: 835–843.

    Article  CAS  Google Scholar 

  18. Franklin J, Tesch H, Hansmann ML, Diehl V . Lymphocyte predominant Hodgkin's disease: pathology and clinical implication. Ann Oncol 1998; 9 (Suppl 5): S39–S44.

    Article  Google Scholar 

  19. El WA, Akhtar S, Mourad WA, Ajarim D, Abdelsalm M, Khafaga Y et al. T-cell/histiocyte-rich B-cell lymphoma: clinical presentation, management and prognostic factors: report on 61 patients and review of literature. Leuk Lymphoma 2007; 48: 1764–1773.

    Article  Google Scholar 

  20. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 2005; 102: 18538–18543.

    Article  CAS  Google Scholar 

  21. Ohtani H . Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer. Cancer Immun 2007; 7: 4.

    PubMed  PubMed Central  Google Scholar 

  22. Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med 2002; 137: 156–163.

    Article  Google Scholar 

  23. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J . Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol 2008; 26: 2505–2511.

    Article  Google Scholar 

  24. Sloand EM, Rezvani K . The role of the immune system in myelodysplasia: implications for therapy. Semin Hematol 2008; 45: 39–48.

    Article  CAS  Google Scholar 

  25. Barrett AJ . Myelodysplastic syndrome—an example of misguided immune surveillance? Leuk Res 2004; 28: 1123–1124.

    Article  Google Scholar 

  26. Gannage M, Abel M, Michallet AS, Delluc S, Lambert M, Giraudier S et al. Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy. J Immunol 2005; 174: 8210–8218.

    Article  CAS  Google Scholar 

  27. Barrett AJ, Rezvani K . Translational mini-review series on vaccines: peptide vaccines for myeloid leukaemias. Clin Exp Immunol 2007; 148: 189–198.

    Article  CAS  Google Scholar 

  28. Molldrem JJ . Vaccination for leukemia. Biol Blood Marrow Transplant 2006; 12: 13–18.

    Article  Google Scholar 

  29. Rezvani K, Grube M, Brenchley JM, Sconocchia G, Fujiwara H, Price DA et al. Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation. Blood 2003; 102: 2892–2900.

    Article  CAS  Google Scholar 

  30. Rezvani K, Brenchley JM, Price DA, Kilical Y, Gostick E, Sewell AK et al. T-cell responses directed against multiple HLA-A*0201-restricted epitopes derived from Wilms' tumor 1 protein in patients with leukemia and healthy donors: identification, quantification, and characterization. Clin Cancer Res 2005; 11: 8799–8807.

    Article  CAS  Google Scholar 

  31. Morita Y, Heike Y, Kawakami M, Miura O, Nakatsuka S, Ebisawa M et al. Monitoring of WT1-specific cytotoxic T lymphocytes after allogeneic hematopoietic stem cell transplantation. Int J Cancer 2006; 119: 1360–1367.

    Article  CAS  Google Scholar 

  32. Einsele H, Ehninger G, Schneider EM, Kruger GF, Vallbracht A, Dopfer R et al. High frequency of graft-versus-host-like syndromes following syngeneic bone marrow transplantation. Transplantation 1988; 45: 579–585.

    Article  CAS  Google Scholar 

  33. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  Google Scholar 

  34. Gahrton G, Svensson H, Bjorkstrand B, Apperley J, Carlson K, Cavo M et al. Syngeneic transplantation in multiple myeloma—a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1999; 24: 741–745.

    Article  CAS  Google Scholar 

  35. Barrett AJ, Ringden O, Zhang MJ, Bashey A, Cahn JY, Cairo MS et al. Effect of nucleated marrow cell dose on relapse and survival in identical twin bone marrow transplants for leukemia. Blood 2000; 95: 3323–3327.

    CAS  PubMed  Google Scholar 

  36. Hess AD, Jones RJ, Morris LE, Noga SJ, Vogelsang GB, Santos GW . Autologous graft-versus-host disease: a novel approach for antitumor immunotherapy. Hum Immunol 1992; 34: 219–224.

    Article  CAS  Google Scholar 

  37. Lewalle P, Hensel N, Guimaraes A, Couriel D, Jiang YZ, Mavroudis D et al. Helper and cytotoxic lymphocyte responses to chronic myeloid leukaemia: implications for adoptive immunotherapy with T cells. Br J Haematol 1996; 92: 587–594.

    CAS  PubMed  Google Scholar 

  38. Molldrem JJ, Lee PP, Kant S, Wieder E, Jiang W, Lu S et al. Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. J Clin Invest 2003; 111: 639–647.

    Article  CAS  Google Scholar 

  39. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000; 6: 1018–1023.

    Article  CAS  Google Scholar 

  40. Marin D, Kaeda J, Szydlo R, Saunders S, Fleming A, Howard J et al. Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukaemia and prognostic factors for cytogenetic relapse. Leukemia 2005; 19: 507–512.

    Article  CAS  Google Scholar 

  41. Mustjoki S, Lundan T, Knuutila S, Porkka K . Appearance of bone marrow lymphocytosis predicts an optimal response to imatinib therapy in patients with chronic myeloid leukemia. Leukemia 2007; 21: 2363–2368.

    Article  CAS  Google Scholar 

  42. Mughal TI, Goldman JM . Molecularly targeted treatment of chronic myeloid leukemia: beyond the imatinib era. Front Biosci 2006; 11: 209–220.

    Article  CAS  Google Scholar 

  43. Powles R, Singhal S, Treleaven J, Kulkarni S, Horton C, Mehta J . Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood 1998; 91: 3481–3486.

    CAS  PubMed  Google Scholar 

  44. Savani BN, Rezvani K, Mielke S, Montero A, Kurlander R, Carter CS et al. Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2006; 107: 1688–1695.

    Article  CAS  Google Scholar 

  45. Savani BN, Mielke S, Rezvani K, Montero A, Yong AS, Wish L et al. Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 1216–1223.

    Article  Google Scholar 

  46. Savani BN, Mielke S, Adams S, Uribe M, Rezvani K, Yong AS et al. Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia 2007; 21: 2145–2152.

    Article  CAS  Google Scholar 

  47. Porrata LF, Gertz MA, Inwards DJ, Litzow MR, Lacy MQ, Tefferi A et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma. Blood 2001; 98: 579–585.

    Article  CAS  Google Scholar 

  48. Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Gastineau DA et al. Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study. Biol Blood Marrow Transplant 2008; 14: 807–816.

    Article  Google Scholar 

  49. Porrata LF, Inwards DJ, Micallef IN, Ansell SM, Geyer SM, Markovic SN . Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease. Br J Haematol 2002; 117: 629–633.

    Article  Google Scholar 

  50. Porrata LF, Litzow MR, Tefferi A, Letendre L, Kumar S, Geyer SM et al. Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. Leukemia 2002; 16: 1311–1318.

    Article  CAS  Google Scholar 

  51. Porrata LF, Markovic SN . Timely reconstitution of immune competence affects clinical outcome following autologous stem cell transplantation. Clin Exp Med 2004; 4: 78–85.

    Article  CAS  Google Scholar 

  52. Behl D, Porrata LF, Markovic SN, Letendre L, Pruthi RK, Hook CC et al. Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia. Leukemia 2006; 20: 29–34.

    Article  CAS  Google Scholar 

  53. De Angulo G, Yuen C, Palla SL, Anderson PM, Zweidler-McKay PA . Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies. Cancer 2008; 112: 407–415.

    Article  CAS  Google Scholar 

  54. Hudson G, Lomas C, Manley S, Caswell M, McDowell H, Pizer B et al. Early lymphocyte regeneration predicts improved survival in childhood acute lymphoblastic leukaemia (abstract). Blood 2003; 102: 1391.

    Google Scholar 

  55. Lomas C, Hudson G, Manley S, Caswell M, McDowell H, Pizer B et al. Early lymphocyte regeneration predicts improved survival in childhood acute myeloid leukaemia (abstract). Blood 2003; 102: 3250.

    Google Scholar 

  56. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850–854.

    Article  CAS  Google Scholar 

  57. Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE et al. Lenalidomide response in relapsed/refractory aggressive non-Hodgkin's lymphoma is related to tumor burden and time from rituximab treatment. ASH Annu Meet Abstr 2007; 110: 2565.

    Google Scholar 

  58. Witzig TE, Reeder CB, Polikoff J, Chowhan NM, Esseessee I, Greenberg R et al. Initial results from an international study in relapsed/refractory aggressive non-Hodgkin's lymphoma to confirm the activity, safety and criteria for predicting response to lenalidomide monotherapy. ASH Annu Meet Abstr 2007; 110: 2572.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stem Cell Allotransplantation Section, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    A J Barrett

  2. Hematology and Stem Cell Transplant Section, Veterans Affairs Medical Center and Vanderbilt University Transplant program, Nashville, TN, USA

    B N Savani

Authors
  1. A J Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B N Savani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A J Barrett.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrett, A., Savani, B. Does chemotherapy modify the immune surveillance of hematological malignancies?. Leukemia 23, 53–58 (2009). https://doi.org/10.1038/leu.2008.273

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2008.273

Keywords

This article is cited by

Search

Advanced search

Quick links