Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion

Roya D. Dadmarz, Aida Ordoubadi, Arnold Mixon, Carolyn O. Thompson, Kathleen C. Barracchini, Yasmine M. Hijazi, Michael A. Steller, Steven A. Rosenberg, Douglas J. Schwartzentruber

Research output: Contribution to journalArticle

Abstract

PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lytic for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243. CONCLUSION: We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalCancer Journal from Scientific American
Volume2
Issue number5
StatePublished - 1996
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Ovarian Neoplasms
Neoplasms
Lymphocytes
Cytokines
Immunoglobulin Isotypes
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Human Herpesvirus 4
Ascites
Immunotherapy
Blood Cells
B-Lymphocytes
Tumor Necrosis Factor-alpha
Fibroblasts
Carcinoma
Phenotype

Keywords

  • Cytokines
  • Human
  • MHC
  • T lymphocytes
  • TAL
  • TIL
  • Tumor immunity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dadmarz, R. D., Ordoubadi, A., Mixon, A., Thompson, C. O., Barracchini, K. C., Hijazi, Y. M., ... Schwartzentruber, D. J. (1996). Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion. Cancer Journal from Scientific American, 2(5), 263-272.

Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion. / Dadmarz, Roya D.; Ordoubadi, Aida; Mixon, Arnold; Thompson, Carolyn O.; Barracchini, Kathleen C.; Hijazi, Yasmine M.; Steller, Michael A.; Rosenberg, Steven A.; Schwartzentruber, Douglas J.

In: Cancer Journal from Scientific American, Vol. 2, No. 5, 1996, p. 263-272.

Research output: Contribution to journalArticle

Dadmarz, RD, Ordoubadi, A, Mixon, A, Thompson, CO, Barracchini, KC, Hijazi, YM, Steller, MA, Rosenberg, SA & Schwartzentruber, DJ 1996, 'Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion', Cancer Journal from Scientific American, vol. 2, no. 5, pp. 263-272.
Dadmarz, Roya D. ; Ordoubadi, Aida ; Mixon, Arnold ; Thompson, Carolyn O. ; Barracchini, Kathleen C. ; Hijazi, Yasmine M. ; Steller, Michael A. ; Rosenberg, Steven A. ; Schwartzentruber, Douglas J. / Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion. In: Cancer Journal from Scientific American. 1996 ; Vol. 2, No. 5. pp. 263-272.
@article{36c9d7227d2946d69c1156222a646728,
title = "Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion",
abstract = "PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lytic for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243. CONCLUSION: We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.",
keywords = "Cytokines, Human, MHC, T lymphocytes, TAL, TIL, Tumor immunity",
author = "Dadmarz, {Roya D.} and Aida Ordoubadi and Arnold Mixon and Thompson, {Carolyn O.} and Barracchini, {Kathleen C.} and Hijazi, {Yasmine M.} and Steller, {Michael A.} and Rosenberg, {Steven A.} and Schwartzentruber, {Douglas J.}",
year = "1996",
language = "English (US)",
volume = "2",
pages = "263--272",
journal = "Cancer journal (Sudbury, Mass.)",
issn = "0765-7846",
publisher = "Association Pour le Developpement de la Communication Cancerologique",
number = "5",

}

TY - JOUR

T1 - Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion

AU - Dadmarz, Roya D.

AU - Ordoubadi, Aida

AU - Mixon, Arnold

AU - Thompson, Carolyn O.

AU - Barracchini, Kathleen C.

AU - Hijazi, Yasmine M.

AU - Steller, Michael A.

AU - Rosenberg, Steven A.

AU - Schwartzentruber, Douglas J.

PY - 1996

Y1 - 1996

N2 - PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lytic for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243. CONCLUSION: We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.

AB - PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lytic for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243. CONCLUSION: We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.

KW - Cytokines

KW - Human

KW - MHC

KW - T lymphocytes

KW - TAL

KW - TIL

KW - Tumor immunity

UR - http://www.scopus.com/inward/record.url?scp=0000052318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0000052318&partnerID=8YFLogxK

M3 - Article

C2 - 9166543

AN - SCOPUS:0000052318

VL - 2

SP - 263

EP - 272

JO - Cancer journal (Sudbury, Mass.)

JF - Cancer journal (Sudbury, Mass.)

SN - 0765-7846

IS - 5

ER -