| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637;
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213; and
Biogen, Cambridge, MA 02142
Metastatic disease is the major cause of morbidity and mortality in cancer. Although surgery, chemotherapy, or radiation can often control primary tumor growth, successful eradication of disseminated metastases remains rare. We have now tested whether direct targeting tumor tissues to generate antitumor immune response before surgical excision produces sufficient CTL against micrometastases. One unsolved problem is whether such response allows coming CTL to be educated and then exit the tumor site. Another unsolved problem is whether these CTL can then patrol and effectively eliminate spontaneously metastasized tumor cells in the periphery. In this study, we have shown that adenovirus-expressing TNFSF14 [LIGHT (name derived from homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes); Ad-LIGHT] inoculated directly into primary 4T1 tumor, a highly aggressive, spontaneously metastasizing mammary carcinoma, followed by surgical removal of the primary tumor can eradicate established and disseminated metastatic tumor cells in the peripheral tissues. Furthermore, we clearly show with a fibrosarcoma model Ag104Ld that local treatment can generate plenty of tumor-specific CTL that exit the primary tumor and infiltrate distal tumors to completely eradicate distal tumors. Therefore, targeting the primary tumor with Ad-LIGHT before surgical excision is a new strategy to elicit better immune response for the eradication of spontaneous metastases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health (NIH) (AI062026, CA115540, and CA09296). P.Y. is a recipient of an NIH Training Grant (5T32DK07074) and Digestive Diseases Research Core Center Seeding Grant P30-DK42086.
2 Address correspondence and reprint requests to Dr. Ping Yu, Department of Pathology and Committee on Immunology, University of Chicago, 5841 South Maryland, MC3083, Chicago, IL 60637; E-mail address: pingyu{at}uchicago.edu or Dr. Yang-Xin Fu, Department of Pathology and Committee on Immunology, University of Chicago, 5841 South Maryland, MC3083, Chicago, IL 60637; E-mail address: yfu{at}uchicago.edu
3 Abbreviations used in this paper: LT
R, lymphotoxin receptor; HVEM, herpesvirus entry mediatior; Ad-LIGHT, adenovirus-expressing LIGHT; mmLIGHT, mutant murine LIGHT; LN, lymph node; DLN, draining LN; NDLN, nondraining LN; SPL, spleen.
This article has been cited by other articles:
|
|
 |
|
  Y. Lee, S. L. Auh, Y. Wang, B. Burnette, Y. Wang, Y. Meng, M. Beckett, R. Sharma, R. Chin, T. Tu, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment Blood, July 16, 2009; 114(3): 589 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Harlin, Y. Meng, A. C. Peterson, Y. Zha, M. Tretiakova, C. Slingluff, M. McKee, and T. F. Gajewski Chemokine Expression in Melanoma Metastases Associated with CD8+ T-Cell Recruitment Cancer Res., April 1, 2009; 69(7): 3077 - 3085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jackaman, A. M. Lew, Y. Zhan, J. E. Allan, B. Koloska, P. T. Graham, B. W. S. Robinson, and D. J. Nelson Deliberately provoking local inflammation drives tumors to become their own protective vaccine site Int. Immunol., November 1, 2008; 20(11): 1467 - 1479. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
