Effects of murine tumor class i major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes

Jeffrey S. Weber, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme-digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1, 000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferony and human recombinant tumor necrosis factor α in vivo, when administered with recombinant interferon γ and recombinant tumor necrosis factor a, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression. [J Natl Cancer Inst 82: 755-761, 1990]

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalJournal of the National Cancer Institute
Volume82
Issue number9
DOIs
StatePublished - May 2 1990
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Lymphocytes
Major Histocompatibility Complex
Tumors
Tumor
Neoplasms
Interleukin-2
Interleukin
Dose
Class
Melanoma
Tumor Necrosis Factor
MHC Class I Genes
Therapeutic Uses
Bearings (structural)
Interferons
Regression

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

Effects of murine tumor class i major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes. / Weber, Jeffrey S.; Rosenberg, Steven A.

In: Journal of the National Cancer Institute, Vol. 82, No. 9, 02.05.1990, p. 755-761.

Research output: Contribution to journalArticle

@article{1a3f8dd1ac42413780eac6595176427e,
title = "Effects of murine tumor class i major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes",
abstract = "Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme-digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1, 000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferony and human recombinant tumor necrosis factor α in vivo, when administered with recombinant interferon γ and recombinant tumor necrosis factor a, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression. [J Natl Cancer Inst 82: 755-761, 1990]",
author = "Weber, {Jeffrey S.} and Rosenberg, {Steven A.}",
year = "1990",
month = "5",
day = "2",
doi = "10.1093/jnci/82.9.755",
language = "English (US)",
volume = "82",
pages = "755--761",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Effects of murine tumor class i major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes

AU - Weber, Jeffrey S.

AU - Rosenberg, Steven A.

PY - 1990/5/2

Y1 - 1990/5/2

N2 - Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme-digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1, 000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferony and human recombinant tumor necrosis factor α in vivo, when administered with recombinant interferon γ and recombinant tumor necrosis factor a, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression. [J Natl Cancer Inst 82: 755-761, 1990]

AB - Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme-digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1, 000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferony and human recombinant tumor necrosis factor α in vivo, when administered with recombinant interferon γ and recombinant tumor necrosis factor a, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression. [J Natl Cancer Inst 82: 755-761, 1990]

UR - http://www.scopus.com/inward/record.url?scp=0025332036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025332036&partnerID=8YFLogxK

U2 - 10.1093/jnci/82.9.755

DO - 10.1093/jnci/82.9.755

M3 - Article

C2 - 2109092

AN - SCOPUS:0025332036

VL - 82

SP - 755

EP - 761

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 9

ER -