Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human γδ-T cells: Implications in the design of γδ-T-cell-based immunotherapies for pancreatic cancer

gamma delta-T cells can recognize and kill malignant cells, particularly those of epithelial origin, through mechanisms which do not require the recognition of tumor-specific antigens (innate immune response). This natural ability of gamma delta-T cells to kill tumor cells in a tumor antigen-independent manner provides a strong rationale for developing clinical trials designed to exploit the innate antitumor properties of gamma delta-T cells. In vitro studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human gamma delta-T cells. The capacity of gamma delta-T cells to bind to as well as to kill pancreatic cancer cells correlated with the degree of surface expression of key intercellular adhesion molecules (ICAM) present on pancreatic cancer cells. Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound poorly by gamma delta-T cells and were found to be resistant to gamma delta-T-cell killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2, gamma delta-T cells were then able to bind to and subsequently kill these cells. In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic cancer cells is critically important in determining the extent to which these cells are sensitive to killing by human gamma delta-T cells. Accordingly, in ongoing and future clinical studies using gamma delta-T cells for the treatment of a variety of epithelial-derived solid tumors-including pancreatic cancer-interventions intended to modulate ICAM expression on tumor cells may become important adjuncts to gamma delta-T-cell-based immunotherapies.