%0 Journal Article %J Clin Exp Immunol %D 1996 %T Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas. %A Roussel, E %A Gingras, M C %A Grimm, E A %A Bruner, J M %A Moser, R P %K Genes, Immunoglobulin %K Glioma %K Humans %K Integrin beta1 %K Intercellular Adhesion Molecule-1 %K L-Selectin %K Lewis X Antigen %K Lymphocytes, Tumor-Infiltrating %K Lymphokines %K Polymerase Chain Reaction %K Receptors, Interleukin-2 %K RNA, Messenger %K Th2 Cells %X

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.

%B Clin Exp Immunol %V 105 %P 344-52 %8 1996 Aug %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/8706344?dopt=Abstract %R 10.1046/j.1365-2249.1996.d01-753.x %0 Journal Article %J Cancer Immunol Immunother %D 1995 %T High expression of adhesion molecules/activation markers with little interleukin-2, interferon gamma, and tumor necrosis factor beta gene activation in fresh tumor-infiltrating lymphocytes from lung adenocarcinoma. %A Roussel, E %A Marie-Claude Gingras %A Grimm, E A %A Roth, J A %K Adenocarcinoma %K Cell Adhesion Molecules %K Gene Expression Regulation, Neoplastic %K Humans %K Immunophenotyping %K Integrins %K Lung Neoplasms %K Lymphocyte Activation %K Lymphocytes, Tumor-Infiltrating %K Lymphokines %K Receptors, Interleukin-2 %K RNA, Messenger %K Transcriptional Activation %X

Little is known about the activation level of tumor-infiltrating lymphocytes (TIL) in human lung adenocarcinoma. We investigated the activation of fresh TIL at cellular and molecular levels and compared it with autologous and healthy normal peripheral blood lymphocytes (PBL) for baseline level. TIL were extracted from 12 primary lung adenocarcinomas by mechanical disruption without enzyme use and isolated by double-density Ficoll gradients. Flow-cytometry analysis of TIL subset distribution revealed that the majority was composed of T lymphocytes, and double labeling with alpha-CD3 and adhesion/activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, each of which was almost absent in autologous T peripheral blood lymphocytes (T-PBL). Moreover, the proportions of T-TIL expressing CD58, CD65, or CD25 were increased severalfold compared to T-PBL. Lymphokine gene activation in TIL was assessed by mRNA reverse transcriptase/polymerase chain reaction (RT-PCR) and primers for interleukin(IL)-2, IL-4, interferon (IFN) gamma, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF) beta. Semiquantitative comparisons between patients' TIL and PBL and healthy normal and activated PBL were performed by computerized image analysis. RT-PCR gel band products were quantified in relative units as a function of their size and intensity. TIL expressed detectable lymphokine mRNA but seemed poorly activated with respect to the total number of lymphokine genes and the amount of mRNA compared with alpha-CD3-activated healthy PBL. IL-2, IFN gamma, and TNF beta did not appear to be expressed at higher levels in TIL than in autologous or healthy normal PBL. However, two-thirds of the patients had TIL distinguishable from autologous PBL by specific expression of GM-CSF and from healthy normal PBL by expression of IL-4. These results show that lung adenocarcinoma TIL populations had little lymphokine gene activation despite the presence of several T cell subsets expressing different adhesion/activation markers. The lack or deficient combination of lymphokine production may be a factor that prevented efficient activation of TIL in these tumors.

%B Cancer Immunol Immunother %V 41 %P 1-9 %8 1995 Jul %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/7641214?dopt=Abstract %R 10.1007/BF01788953