Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas.

TitlePredominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas.
Publication TypeJournal Article
Year of Publication1996
AuthorsRoussel, E, Gingras, MC, Grimm, EA, Bruner, JM, Moser, RP
JournalClin Exp Immunol
Volume105
Issue2
Pagination344-52
Date Published1996 Aug
ISSN0009-9104
KeywordsGenes, Immunoglobulin, Glioma, Humans, Integrin beta1, Intercellular Adhesion Molecule-1, L-Selectin, Lewis X Antigen, Lymphocytes, Tumor-Infiltrating, Lymphokines, Polymerase Chain Reaction, Receptors, Interleukin-2, RNA, Messenger, Th2 Cells
Abstract

Increasing evidence suggests the existence of polarized human T cell responses described as Th1-type (promoting cell-mediated immunity) and Th2-type (promoting humoral immunity), characterized by a dominant production of either interferon-gamma (IFN-gamma) or IL-4, respectively. Little is known about the intratumoural activation of infiltrating lymphocytes (TIL) in human gliomas. Therefore, we assessed fresh TIL at cellular and molecular levels to find out if they were activated and polarized into a type 1 or 2 immune response. Flow cytometry analysis of TIL revealed that the major subset was made of T lymphocytes. Double labelling with alpha-CD3 and adhesion/ activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, some of which were almost absent in autologous T peripheral blood lymphocytes (T-PBL). Furthermore, the proportions of T-TIL expressing CD56, CD65, or CD25 were several-fold higher than in T-PBL. Intratumoural functional activation of TIL was tested by semiquantitative assessment in relative units (RU) of lymphokine gene activation with mRNA reverse transcriptase-polymerase chain reaction (RT-PCR). All TIL populations except one significantly expressed IL-4 1 to 2 logs of RU above healthy PBL baseline. Similarly, all patients expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) in a range comparable to IL-4. However, most TIL populations did not express IFN-gamma, IL-2, and tumour necrosis factor-beta (TNF-beta) at higher levels than healthy normal PBL. The increase proportion of T cells expressing activation markers and the consistent detection of significant IL-4 and GM-CSF lymphokine gene activation in TIL populations suggested a predominant type 2 intratumoural immune response that does not promote cell-mediated tumouricidal activity and may contribute to the inefficiency of the antiglioma immune response.

DOI10.1046/j.1365-2249.1996.d01-753.x
Alternate JournalClin. Exp. Immunol.
PubMed ID8706344
PubMed Central IDPMC2200505
Grant List1 T32 HL07747-02 / HL / NHLBI NIH HHS / United States