Impairment of T-cell activation in head and neck cancer in situ and in vitro - Strategies for an immune restoration

Background: The rationale for the study was based on the hypothesis that de creased or absent expression on tumor sells of adhesion molecules, the clas s I or class II major histocompatibility complex (MHC) molecules, or costim ulatory molecules might be responsible, in part, for the poor ability of sq uamous cell carcinoma of the head and neck (SCCHN) to induce generation of anti-tumor effector cells in vitro and in vivo. Objective: To investigate expression of intercellular adhesion molecule-1 I CAM-1) and lymphocyte function associated antigen-3 (LFA-3) and distributio n of the co-stimulatory molecules, B7.1, B7.2, and CD40, and of class I and class II MHC molecules on SCCHN cells in situ and on SCCHN cell lines. Setting: University medical centers. Design: Expression of ICAM-1, LFA-3, MHC molecules, B7.1, B7.2, and CD40 wa s evaluated in human SCCHN biopsy specimens by immunohistochemistry and on SCCHN cell lines by flow cytometry. To confirm our hypothesis that impaired T-cell activation observed in patients with SCCHN is caused by the absence of costimulatory B7 molecules, a B7-negative SCCHN cell line was transduce d with the B7.1 gene, using a retroviral vector, and tested in mixed lympho cyte tumor cocultures. Results: In contrast to abundant expression of ICAM-1, LFA-3, class I MHC m olecules, and CD40, the absence of B7.1, B7.2, and class II MHC molecules o n tumor cells was observed in situ and in vitro. Lymphocytes and antigen-pr esenting cells in inflammatory infiltrates surrounding tumor cell clusters expressed both costimulatory and adhesion molecules. The SCCHN lines negati ve for B7.1 and class II MHC antigens failed to induce proliferation of T c ells in mixed lymphocyte tumor cocultures. However, when these cell lines w ere transduced with the B7.1 gene, their ability to induce T-cell prolifera tion in mixed lymphocyte tumor cocultures was restored. Conclusions;: The absence of B7 protein or class II MHC antigen expression on human SCCHN cells is responsible for the failure of these tumors to indu ce proliferation of T cells in vitro. Transduction of the B7.1 gene into SC CHN restores the ability of the tumor to induce T-cell proliferation in vit ro.