Graft-versus-tumor effect

Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells (T lymphocytes) that can be beneficial for the recipient by eliminating residual malignant cells.[1] GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies.[2] This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer.[3] It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect.[4] The biology of GvT response is still not fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved.[5][6] This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers (NK cells) as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.[6]

  1. ^ Thompson LF, Tsukamoto H, Chernogorova P, Zeiser R (January 2013). "A delicate balance: CD73-generated adenosine limits the severity of graft vs. host disease but also constrains the allogeneic graft vs. tumor effect". Oncoimmunology. 2 (1): e22107. doi:10.4161/onci.22107. PMC 3583907. PMID 23482243.
  2. ^ Kolb HJ (December 2008). "Graft-versus-leukemia effects of transplantation and donor lymphocytes". Blood. 112 (12): 4371–83. doi:10.1182/blood-2008-03-077974. PMID 19029455.
  3. ^ Childs RW, Clave E, Tisdale J, Plante M, Hensel N, Barrett J (July 1999). "Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral-blood progenitor-cell transplant: evidence for a graft-versus-tumor effect". Journal of Clinical Oncology. 17 (7): 2044–9. doi:10.1200/jco.1999.17.7.2044. PMID 10561256.
  4. ^ Vagianos C, Polydorou A, Karatzas T, Vagenas C, Stavropoulos M, Androulakis J (1992). "Successful treatment of postoperative external biliary fistula by selective nasobiliary drainage". HPB Surgery. 6 (2): 115–20, discussion 120–4. doi:10.1155/1992/58436. PMC 2443016. PMID 1292584.
  5. ^ Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, et al. (March 2005). "Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning". Journal of Clinical Oncology. 23 (9): 1993–2003. doi:10.1200/JCO.2005.08.136. hdl:2268/102049. PMID 15774790.
  6. ^ a b Rezvani AR, Storb RF (May 2008). "Separation of graft-vs.-tumor effects from graft-vs.-host disease in allogeneic hematopoietic cell transplantation". Journal of Autoimmunity. 30 (3): 172–9. doi:10.1016/j.jaut.2007.12.002. PMC 2329571. PMID 18242060.