Functional analysis of TCR γδ+ T cells in tumour-infiltrating lymphocytes (TIL) of human pancreatic cancer

Abstract

In six patients with advanced pancreatic carcinoma, TIL and tumour-draining lymphocytes (TDL) were isolated from primary pancreatic tumour and regional lymph nodes. In comparison with TDL and peripheral blood lymphocytes (PBL), TIL contained a comparatively higher percentage of TCR gamma delta+ cells, although they were still a small fraction. By 2 weeks culture with rIL-2 and immobilized OKT-3 antibody, the TCR gamma delta+ cells in TIL were preferentially expanded at the early culture periods, although it was temporary. In four cases, the TCR gamma delta+ and CD8+ TCR alpha beta+ TIL were separated by negative sorting using flowcytometry. All the TCR gamma delta+ TIL were CD4-, CD8- (double negative), and one of the TIL lines was mostly composed of delta TCS1+ cells, while the others were delta TCS1-. In comparison with CD8+ TCR alpha beta+ TIL, all the TCR gamma delta+ TIL exhibited much stronger lytic activity against freshly isolated autologous pancreatic cancer cells. However, all the gamma delta+ TIL also exhibited a strong non-MHC-restricted cytotoxicity, and there was no correlation between the lytic pattern and the percentage of delta TCS1+ cells. These data suggest that the TCR gamma delta+ T cells can proliferate vigorously in a certain condition, and if successfully expanded in vitro they might be helpful material for effective adoptive immunotherapy.

Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging

“…Interestingly, the A3D8 anti CD44 antibody that did not block HA binding to CD44, inhibited cell migration in our model and in other models (12,51), probably by preventing CD44 conformation changes induced by HA binding. However, in other systems it did not affect migration (53). Other pathways involving VCAM and ICAM proteins could control the migratory capability of AoSMCs.…”

Expansion and Immunological Study of Human Tumor Infiltrating Gamma/Delta T Lymphocytes in vitro¹

“…Preferential expansion and antitumor responses of subsets of γ/δ TILs have been found in many kinds of cancer, including colorectal cancer [4, 5], lung adenocarcinoma [6, 7]and pancreatic cancer [8]. Such γ/δ T cells demonstrated a non–MHC–restricted recognition and cytolytic activity to autologous/allogeneic tumor cell lines.…”

Vγ9Vδ2 T Cell Response to Colon Carcinoma Cells

“…Nonetheless, the tumor ligands recognized by these subsets are likely to be distinct. Indeed, although V␦1 T cells derived from TIL kill a wide array of solid tumors (7)(8)(9)(10)(11), V␥9V␦2 T cells preferentially kill hemopoietic tumor cell lines, such as myeloma, lymphoma, and erythroleukemia (12)(13)(14)(15). However, more recent studies reported recognition of some melanoma and renal carcinoma cell lines by V␥9V␦2 T cells and killing of autologous metastatic renal carcinoma cells (RCC) by autologous PBL-derived V␥9V␦2 T cell lines (16 -18).…”