| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Mechanisms That Cannot Be Predicted From In Vitro T Cell Characteristics1
Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, OH 44195
Experimental pulmonary metastases have been successfully treated by
adoptive transfer of tumor-sensitized T cells from perforin knockout
(KO) or Fas/APO-1 ligandKO mice, suggesting a prominent
role for secretion of cytokines such as IFN-
. In the present study
we confirmed that rejection of established methylcholanthrene-205
(MCA-205) pulmonary metastases displayed a requirement for T cell
IFN- expression. However, this requirement could be obviated by
transferring larger numbers of tumor-sensitized IFN- KO
T cells or by immunosensitizing sublethal irradiation (500 rad) of the
host before adoptive therapy. Extrapulmonary tumors (MCA-205 s.c. and
intracranial) that required adjunct sublethal irradiation for treatment
efficacy also displayed no requirement for host or T cell expression of
IFN-. Nonetheless, rejection of MCA-205 s.c. tumors and i.p. EL-4
tumors, but not MCA-205 pulmonary or intracranial tumors, displayed a
significant requirement for T cell perforin expression (i.e., CTL
participation). The capacity of T cells to lyse tumor targets and
secrete IFN- in vitro before adoptive transfer was nonpredictive of
the roles of these activities in subsequent tumor rejection. Adoptive
therapy studies employing KO mice are therefore indispensable for
revealing a diversity of tumor rejection mechanisms that may lack in
vitro correlation due to delays in their induction. Seemingly
contradictory KO data from different studies are reconciled by the
capacity of anti-tumor T cells to rely on alternative mechanisms
when treated in larger numbers, the variable participation of CTL at
different anatomic locations of tumor, and the apparent capacity of
sublethal irradiation to provide a therapeutic alternative to host or T
cell IFN- production.
This article has been cited by other articles:
|
|
 |
|
  M. Moeller, M. H. Kershaw, R. Cameron, J. A. Westwood, J. A. Trapani, M. J. Smyth, and P. K. Darcy Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CD8+ T Cells Cancer Res., December 1, 2007; 67(23): 11428 - 11437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. MacGregor, Q. Li, A. E. Chang, T. M. Braun, D. P.M. Hughes, and K. T. McDonagh Ex vivo Culture with Interleukin (IL)-12 Improves CD8+ T-Cell Adoptive Immunotherapy for Murine Leukemia Independent of IL-18 or IFN-{gamma} but Requires Perforin. Cancer Res., May 1, 2006; 66(9): 4913 - 4921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Hollenbaugh, J. Reome, M. Dobrzanski, and R. W. Dutton The Rate of the CD8-Dependent Initial Reduction in Tumor Volume Is Not Limited by Contact-Dependent Perforin, Fas Ligand, or TNF-Mediated Cytolysis J. Immunol., August 1, 2004; 173(3): 1738 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Caldwell, M. H. Ryan, E. McDuffie, and S. I. Abrams The Fas/Fas Ligand Pathway Is Important for Optimal Tumor Regression in a Mouse Model of CTL Adoptive Immunotherapy of Experimental CMS4 Lung Metastases J. Immunol., September 1, 2003; 171(5): 2402 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qin, J. Schwartzkopff, F. Pradera, T. Kammertoens, B. Seliger, H. Pircher, and T. Blankenstein A Critical Requirement of Interferon {gamma}-mediated Angiostasis for Tumor Rejection by CD8+ T Cells Cancer Res., July 15, 2003; 63(14): 4095 - 4100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kessler, X. Hong, J. Petrovic, A. Borodovsky, N. P. Dantuma, M. Bogyo, H. S. Overkleeft, H. Ploegh, and R. Glas Pathways Accessory to Proteasomal Proteolysis Are Less Efficient in Major Histocompatibility Complex Class I Antigen Production J. Biol. Chem., March 14, 2003; 278(12): 10013 - 10021. [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]
|
|
|
|
|
|
L. Peng, J. Kjaergaard, G. E. Plautz, M. Awad, J. A. Drazba, S. Shu, and P. A. Cohen Tumor-Induced L-Selectinhigh Suppressor T Cells Mediate Potent Effector T Cell Blockade and Cause Failure of Otherwise Curative Adoptive Immunotherapy J. Immunol., November 1, 2002; 169(9): 4811 - 4821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Seki, A. D. Brooks, C. R. D. Carter, T. C. Back, E. M. Parsoneault, M. J. Smyth, R. H. Wiltrout, and T. J. Sayers Tumor-Specific CTL Kill Murine Renal Cancer Cells Using Both Perforin and Fas Ligand-Mediated Lysis In Vitro, But Cause Tumor Regression In Vivo in the Absence of Perforin J. Immunol., April 1, 2002; 168(7): 3484 - 3492. [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]
|
|
|
|
|
|
M. M. Soares, V. Mehta, and O. J. Finn 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., June 1, 2001; 166(11): 6555 - 6563. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
