Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete
granulocyte-macrophage colony-stimulating factor and tumor necrosis
factor-alpha in response to autologous tumor stimulation
DJ Schwartzentruber, M Stetler-Stevenson, SA Rosenberg and SL Topalian
Surgery Branch, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892.
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-alpha 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.
Volume 82,
Issue 4,
pp. 1204-1211,
08/15/1993
Copyright © 1993 by The American Society of Hematology