Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases

Ping Yu, Youjin Lee, Yang Wang, Xiaojuan Liu, Sogyong Auh, Thomas F. Gajewski, Hans Schreiber, Zhaoyang You, Campbell Kaynor, Xinzhong Wang, Yang Xin Fu

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1960-1968
Number of pages9
JournalJournal of Immunology
Volume179
Issue number3
DOIs
StatePublished - Aug 1 2007

Fingerprint

Neoplasm Metastasis
Neoplasms
Light
Lymphotoxin-alpha
Virus Internalization
Neoplasm Micrometastasis
Fibrosarcoma
Simplexvirus
Adenoviridae
Names
Glycoproteins
Radiation
Breast Neoplasms
Morbidity
T-Lymphocytes
Drug Therapy
Mortality
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases. / Yu, Ping; Lee, Youjin; Wang, Yang; Liu, Xiaojuan; Auh, Sogyong; Gajewski, Thomas F.; Schreiber, Hans; You, Zhaoyang; Kaynor, Campbell; Wang, Xinzhong; Fu, Yang Xin.

In: Journal of Immunology, Vol. 179, No. 3, 01.08.2007, p. 1960-1968.

Research output: Contribution to journalArticle

Yu, P, Lee, Y, Wang, Y, Liu, X, Auh, S, Gajewski, TF, Schreiber, H, You, Z, Kaynor, C, Wang, X & Fu, YX 2007, 'Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases', Journal of Immunology, vol. 179, no. 3, pp. 1960-1968. https://doi.org/10.4049/jimmunol.179.3.1960
Yu, Ping ; Lee, Youjin ; Wang, Yang ; Liu, Xiaojuan ; Auh, Sogyong ; Gajewski, Thomas F. ; Schreiber, Hans ; You, Zhaoyang ; Kaynor, Campbell ; Wang, Xinzhong ; Fu, Yang Xin. / Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases. In: Journal of Immunology. 2007 ; Vol. 179, No. 3. pp. 1960-1968.
@article{d1a9c3fbc43b415ebf323cb1a79eb4bf,
title = "Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases",
abstract = "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.",
author = "Ping Yu and Youjin Lee and Yang Wang and Xiaojuan Liu and Sogyong Auh and Gajewski, {Thomas F.} and Hans Schreiber and Zhaoyang You and Campbell Kaynor and Xinzhong Wang and Fu, {Yang Xin}",
year = "2007",
month = "8",
day = "1",
doi = "10.4049/jimmunol.179.3.1960",
language = "English (US)",
volume = "179",
pages = "1960--1968",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases

AU - Yu, Ping

AU - Lee, Youjin

AU - Wang, Yang

AU - Liu, Xiaojuan

AU - Auh, Sogyong

AU - Gajewski, Thomas F.

AU - Schreiber, Hans

AU - You, Zhaoyang

AU - Kaynor, Campbell

AU - Wang, Xinzhong

AU - Fu, Yang Xin

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548646455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548646455&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.179.3.1960

DO - 10.4049/jimmunol.179.3.1960

M3 - Article

VL - 179

SP - 1960

EP - 1968

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -