Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in response to autologous tumor stimulation

Douglas J. Schwartzentruber, Maryalice Stetler-Stevenson, Steven A. Rosenberg, Suzanne Topalian

Research output: Contribution to journalArticle

Abstract

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% ± 8% CD3+ (mean ± SEM), 47% ± 8% CD4+ and 35% ± 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.

Original languageEnglish (US)
Pages (from-to)1204-1211
Number of pages8
JournalBlood
Volume82
Issue number4
StatePublished - Aug 15 1993
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
Lymphocytes
B-Cell Lymphoma
Granulocyte-Macrophage Colony-Stimulating Factor
Tumors
Tumor Necrosis Factor-alpha
Cells
Neoplasms
Cytokines
Lymphoma
Malignant Pleural Effusion
Cell culture
Immunoglobulin Isotypes
Major Histocompatibility Complex
Interleukin-2
Suspensions
Flow Cytometry
B-Lymphocytes
Lymph Nodes
T-cells

ASJC Scopus subject areas

  • Hematology

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Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in response to autologous tumor stimulation. / Schwartzentruber, Douglas J.; Stetler-Stevenson, Maryalice; Rosenberg, Steven A.; Topalian, Suzanne.

In: Blood, Vol. 82, No. 4, 15.08.1993, p. 1204-1211.

Research output: Contribution to journalArticle

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title = "Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in response to autologous tumor stimulation",
abstract = "Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50{\%} of cells (median) were malignant B cells and 36{\%} were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75{\%} ± 8{\%} CD3+ (mean ± SEM), 47{\%} ± 8{\%} CD4+ and 35{\%} ± 7{\%} CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20{\%} of patients studied.",
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