| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and Granulocyte/Macrophage Colony-Stimulating Factor) Producing Donor Tumor-Infiltrating Lymphocytes1
Laboratory of Biologic Cancer Therapy, Department of Surgery, Division of Surgical Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL)
and systemic low dose rIL-2 effectively eradicates pulmonary metastases
of the murine MCA-105 sarcoma. We described earlier that host
CD8+ T cells are critical for tumor eradication and
that successful treatment is associated with production of high levels
of IFN-
and granulocyte/macrophage (GM)-CSF by donor TIL in vitro.
Here, we propose the mechanism through which adoptively transferred
Thy-1.1+ TIL induce a host antitumor response in congenic
Thy-1.2+ tumor-bearing mice. Donor Thy-1.1+ TIL
were detected at the tumor site 12 h after transfer. These
Thy-1.1+ cells produced IFN- and GM-CSF in situ. The
percentage of Thy-1.1+ TIL at the tumor site increased up
to 16.4 ± 4.9% 24 h after transfer but decreased to
undetectable levels thereafter. In contrast, the percentages of host
cells producing IFN- and GM-CSF continued to increase at the tumor
site. These increases were significantly higher in TIL +
rIL-2-treated mice compared with untreated mice and rIL-2-treated mice
48 h after TIL transfer. The appearance of IFN-+
and GM-CSF+ cells was followed by a large influx of host
CD4+, CD8+, and Thy-1.2+ TIL and
eventually by tumor eradication. This response was tumor specific since
TIL obtained from MCA-205 did not induce high levels of IFN- and
GM-CSF and did not induce tumor eradication of MCA-105 tumor.
Coinjection of Thy-1.1+ TIL and anti-IFN- or
anti-GM-CSF mAb significantly inhibited antitumor efficacy of the
TIL + rIL-2 treatment. We conclude that successful adoptive
immunotherapy in this model is mediated through cytokine production by
adoptively transferred TIL that induce a host T cell-dependent
antitumor response.
This article has been cited by other articles:
|
|
 |
|
  S. Zarei, F. Schwenter, P. Luy, M. Aurrand-Lions, P. Morel, M. Kopf, G. Dranoff, and N. Mach Role of GM-CSF signaling in cell-based tumor immunization Blood, June 25, 2009; 113(26): 6658 - 6668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Zhang, A. Barber, and C. L. Sentman Chimeric NKG2D Modified T Cells Inhibit Systemic T-Cell Lymphoma Growth in a Manner Involving Multiple Cytokines and Cytotoxic Pathways Cancer Res., November 15, 2007; 67(22): 11029 - 11036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Ullenhag, J.-E. Frodin, S. Mosolits, S. Kiaii, M. Hassan, M. C. Bonnet, P. Moingeon, H. Mellstedt, and H. Rabbani Immunization of Colorectal Carcinoma Patients with a Recombinant Canarypox Virus Expressing the Tumor Antigen Ep-CAM/KSA (ALVAC-KSA) and Granulocyte Macrophage Colony- stimulating Factor Induced a Tumor-specific Cellular Immune Response Clin. Cancer Res., July 1, 2003; 9(7): 2447 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Poehlein, H.-M. Hu, J. Yamada, I. Assmann, W. G. Alvord, W. J. Urba, and B. A. Fox TNF Plays an Essential Role in Tumor Regression after Adoptive Transfer of Perforin/IFN-{gamma} Double Knockout Effector T Cells J. Immunol., February 15, 2003; 170(4): 2004 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Haynes, J. A. Trapani, M. W. L. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth, and P. K. Darcy Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors Blood, October 16, 2002; 100(9): 3155 - 3163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Chang, B. G. Redman, J. R. Whitfield, B. J. Nickoloff, T. M. Braun, P. P. Lee, J. D. Geiger, and J. J. Mule A Phase I Trial of Tumor Lysate-pulsed Dendritic Cells in the Treatment of Advanced Cancer Clin. Cancer Res., April 1, 2002; 8(4): 1021 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Winter, H.-M. Hu, K. McClain, W. J. Urba, and B. A. Fox Immunotherapy of Melanoma: A Dichotomy in the Requirement for IFN-{{gamma}} in Vaccine-Induced Antitumor Immunity Versus Adoptive Immunotherapy J. Immunol., June 15, 2001; 166(12): 7370 - 7380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gervois, N. Labarriere, S. Le Guiner, M.-C. Pandolfino, J.-F. Fonteneau, Y. Guilloux, E. Diez, B. Dreno, and F. Jotereau High Avidity Melanoma-reactive Cytotoxic T Lymphocytes Are Efficiently Induced from Peripheral Blood Lymphocytes on Stimulation by Peptide-pulsed Melanoma Cells Clin. Cancer Res., April 1, 2000; 6(4): 1459 - 1467. [Abstract] [Full Text]
|
|
|
|
|
|
H. Winter, H.-M. Hu, W. J. Urba, and B. A. Fox Tumor Regression After Adoptive Transfer of Effector T Cells Is Independent of Perforin or Fas Ligand (APO-1L/CD95L) J. Immunol., October 15, 1999; 163(8): 4462 - 4472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Dobrzanski, J. B. Reome, and R. W. Dutton Therapeutic Effects of Tumor-Reactive Type 1 and Type 2 CD8+ T Cell Subpopulations in Established Pulmonary Metastases J. Immunol., June 1, 1999; 162(11): 6671 - 6680. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
