CD4 T-Helper Responses to the Anaplastic Lymphoma Kinase (ALK) Protein in Patients with ALK-Positive Anaplastic Large-Cell Lymphoma

Abstract

We have previously shown both humoral and CTL responses to anaplastic lymphoma kinase (ALK) in patients with ALK- positive anaplastic large-cell lymphoma (ALCL). However, because CD4 + T-helper (Th) cells also play a vital role in developing and maintaining tumor immunity, we investigated the presence of a CD4 + Th response in ALK-positive ALCL. Using an IFN- ; ELISPOT assay, we identified two ALK-derived DRB1-restricted 24-mer promiscuous peptides, ALK1 278–301 and ALK2 233–256 , as being immunogenic in six ALK-positive ALCL patients but not in two ALK-negative ALCL patients or five normal subjects. A significant interleukin-4 response to the ALK peptides was detected in only one ALK-positive patient. CD4 + Th cell lines lysed ALK-positive ALCL cell lines in a MHC class II–restricted manner. This first report of a CD4 + Th response to ALK provides valuable information for devel- oping future immunotherapeutic options for ALK-positive ALCL patients who fail to respond well to conventional therapies.