Skip to main content
Top
Published in: Tumor Biology 6/2014

01-06-2014 | Research Article

Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment with donor lymphocyte infusion

Authors: Tao Jiang, Daxun Piao, Anlong Zhu, Hongchi Jiang

Published in: Tumor Biology | Issue 6/2014

Login to get access

Abstract

The objective of this study was to detect changes in T lymphocyte subpopulations in mice with CT26 subcutaneous colon cancer after treatment with donor lymphocyte infusion (DLI) and cyclophosphamide (CP) chemotherapy. A colon cancer model was established by subcutaneous injection of CT26 carcinoma cells into BALB/C mice. The mice were randomized into different treatment groups. We recorded survival times, tumor growth inhibition rates, histopathological changes, and T lymphocyte subsets in peripheral blood of the mice. Mice treated with DLI and CP survived 33.5 ± 5.02 days, which was significantly longer than the survival time of untreated control mice (16.7 ± 2.98 days, P < 0.01). In addition, the tumor inhibitory rate was higher in mice treated with DLI and CP (89.3 %) than that in mice treated with CP or DLI alone (67.1 and 34.5 %, respectively). There were higher levels of T lymphocytes that were CD3+ and CD4+ in mice treated with DLI alone or the combination of CP and DLI (P < 0.05), and the ratio of CD4+/CD8+ cells was significantly improved in these mice (P < 0.05). DLI combined with chemotherapy significantly prolonged survival and inhibited tumor growth in mice with CT26 colon cancer. This treatment might also improve immune function in these mice. Donor spleen cells that include high numbers of allogeneic lymphocytes and a few stem cells could induce a graft-versus-tumor effect, leading to elimination of residual cancer cells. This indicates that it is potentially a feasible adoptive cellular immunotherapy strategy for the management of solid tumors.
Literature
1.
go back to reference Wu XY, Huang XE, You SX, Lu YY, Cao J, Liu J. Phase II study of pemetrexed as second or third line combined chemotherapy in patients with colorectal cancer. Asian Pac J Cancer Prev. 2013;14(3):2019–22.CrossRefPubMed Wu XY, Huang XE, You SX, Lu YY, Cao J, Liu J. Phase II study of pemetrexed as second or third line combined chemotherapy in patients with colorectal cancer. Asian Pac J Cancer Prev. 2013;14(3):2019–22.CrossRefPubMed
2.
go back to reference Mohile SG, Hardt M, Tew W, Owusu C, Klepin H, Gross C, et al. Toxicity of bevacizumab in combination with chemotherapy in older patients. Oncologist. 2013;18(4):408–14.PubMedCentralCrossRefPubMed Mohile SG, Hardt M, Tew W, Owusu C, Klepin H, Gross C, et al. Toxicity of bevacizumab in combination with chemotherapy in older patients. Oncologist. 2013;18(4):408–14.PubMedCentralCrossRefPubMed
3.
go back to reference Ye F, Liu Z, Tan A, Liao M, Mo Z, Yang X. XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71(3):733–40.CrossRefPubMed Ye F, Liu Z, Tan A, Liao M, Mo Z, Yang X. XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71(3):733–40.CrossRefPubMed
4.
go back to reference Hodgson KD, Hutchinson AD, Wilson CJ, Nettelbeck T. A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. Cancer Treat Rev. 2013;39(3):297–304.CrossRefPubMed Hodgson KD, Hutchinson AD, Wilson CJ, Nettelbeck T. A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. Cancer Treat Rev. 2013;39(3):297–304.CrossRefPubMed
5.
go back to reference Thomas-Schoemann A, Batteux F, Mongaret C, Nicco C, Chéreau C, Annereau M, et al. Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer. J Immunol. 2012;189(11):5171–7.CrossRefPubMed Thomas-Schoemann A, Batteux F, Mongaret C, Nicco C, Chéreau C, Annereau M, et al. Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer. J Immunol. 2012;189(11):5171–7.CrossRefPubMed
6.
go back to reference Toomey PG, Vohra NA, Ghansah T, Sarnaik AA, Pilon-Thomas SA. Immunotherapy for gastrointestinal malignancies. Cancer Control. 2013;20(1):32–42.PubMed Toomey PG, Vohra NA, Ghansah T, Sarnaik AA, Pilon-Thomas SA. Immunotherapy for gastrointestinal malignancies. Cancer Control. 2013;20(1):32–42.PubMed
7.
go back to reference Lee EM, Hurh S, Cho B, Oh KH, Kim SU, Surh CD, et al. CD70-CD27 ligation between neural stem cells and CD4+ T cells induces Fas-FasL-mediated T cell death. Stem Cell Res Ther. 2013;4(3):56.PubMedCentralCrossRefPubMed Lee EM, Hurh S, Cho B, Oh KH, Kim SU, Surh CD, et al. CD70-CD27 ligation between neural stem cells and CD4+ T cells induces Fas-FasL-mediated T cell death. Stem Cell Res Ther. 2013;4(3):56.PubMedCentralCrossRefPubMed
8.
go back to reference Zinöcker S, Dressel R, Wang XN, Dickinson AM, Rolstad B. Immune reconstitution and graft-versus-host reactions in rat models of allogeneic hematopoietic cell transplantation. Front Immunol. 2012;3:355.PubMedCentralPubMed Zinöcker S, Dressel R, Wang XN, Dickinson AM, Rolstad B. Immune reconstitution and graft-versus-host reactions in rat models of allogeneic hematopoietic cell transplantation. Front Immunol. 2012;3:355.PubMedCentralPubMed
9.
go back to reference Moscovitch M, Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol. 1984;132(2):997–1000.PubMed Moscovitch M, Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol. 1984;132(2):997–1000.PubMed
10.
go back to reference Teshima T, Mach N, Hill GR, Pan L, Gillessen S, Dranoff G, et al. Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res. 2001;61(1):162–71.PubMed Teshima T, Mach N, Hill GR, Pan L, Gillessen S, Dranoff G, et al. Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res. 2001;61(1):162–71.PubMed
11.
go back to reference Porter DL. Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and controversies. Hematology Am Soc Hematol Educ Program. 2011;2011:292–8.CrossRefPubMed Porter DL. Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and controversies. Hematology Am Soc Hematol Educ Program. 2011;2011:292–8.CrossRefPubMed
12.
go back to reference Eibl B, Schwaighofer H, Nachbaur D, Marth C, Gächter A, Knapp R, et al. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996;88(4):1501–8.PubMed Eibl B, Schwaighofer H, Nachbaur D, Marth C, Gächter A, Knapp R, et al. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996;88(4):1501–8.PubMed
13.
go back to reference Petersen SL. Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. Dan Med Bull. 2007;54(2):112–39.PubMed Petersen SL. Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. Dan Med Bull. 2007;54(2):112–39.PubMed
14.
go back to reference Maria M, Avichai S, Nagler A. Regulatory T cells in allogeneic stem cell transplantation. Clin Dev Immunol. 2013;2013:608951. Maria M, Avichai S, Nagler A. Regulatory T cells in allogeneic stem cell transplantation. Clin Dev Immunol. 2013;2013:608951.
15.
go back to reference McIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, et al. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013;98(3):346–52.PubMedCentralCrossRefPubMed McIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, et al. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013;98(3):346–52.PubMedCentralCrossRefPubMed
16.
go back to reference Takeuchi A, Eto M, Yamada H, Tatsugami K, Naito S, Yoshikai Y. A reduction of recipient regulatory T cells by cyclophosphamide contributes to an anti-tumor effect of nonmyeloablative allogeneic stem cell transplantation in mice. Int J Cancer. 2012;130(2):365–76.CrossRefPubMed Takeuchi A, Eto M, Yamada H, Tatsugami K, Naito S, Yoshikai Y. A reduction of recipient regulatory T cells by cyclophosphamide contributes to an anti-tumor effect of nonmyeloablative allogeneic stem cell transplantation in mice. Int J Cancer. 2012;130(2):365–76.CrossRefPubMed
17.
go back to reference Zhang Y, Pan Z, Chen Y, Jie Y, He Y. Specific immunosuppression by mixed chimerism with bone marrow transplantation after Staphylococcal Enterotoxin B pretreatment could prolong corneal allograft survival in mice. Mol Vis. 2012;18:974–82.PubMedCentralPubMed Zhang Y, Pan Z, Chen Y, Jie Y, He Y. Specific immunosuppression by mixed chimerism with bone marrow transplantation after Staphylococcal Enterotoxin B pretreatment could prolong corneal allograft survival in mice. Mol Vis. 2012;18:974–82.PubMedCentralPubMed
18.
19.
go back to reference Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4(124):124ra28.PubMedCentralCrossRefPubMed Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4(124):124ra28.PubMedCentralCrossRefPubMed
20.
go back to reference Gladstone DE, Bolaños-Meade J, Huff CA, Zahurak M, Flinn I, Borrello I, et al. High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. Leuk Lymphoma. 2011;52(11):2076–81.PubMedCentralCrossRefPubMed Gladstone DE, Bolaños-Meade J, Huff CA, Zahurak M, Flinn I, Borrello I, et al. High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. Leuk Lymphoma. 2011;52(11):2076–81.PubMedCentralCrossRefPubMed
21.
go back to reference Wang H, Yang Y, Wang G, Wang S, Yeap BY, Sykes M, et al. Donor bone marrow-derived T cells inhibit GVHD induced by donor lymphocyte infusion in established mixed allogeneic hematopoietic chimeras. PLoS One. 2012;7(10):e47120.PubMedCentralCrossRefPubMed Wang H, Yang Y, Wang G, Wang S, Yeap BY, Sykes M, et al. Donor bone marrow-derived T cells inhibit GVHD induced by donor lymphocyte infusion in established mixed allogeneic hematopoietic chimeras. PLoS One. 2012;7(10):e47120.PubMedCentralCrossRefPubMed
22.
go back to reference Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010;115(21):4293–301.PubMedCentralCrossRefPubMed Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010;115(21):4293–301.PubMedCentralCrossRefPubMed
Metadata
Title
Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment with donor lymphocyte infusion
Authors
Tao Jiang
Daxun Piao
Anlong Zhu
Hongchi Jiang
Publication date
01-06-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1740-4

Other articles of this Issue 6/2014

Tumor Biology 6/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine