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 ALKpositive 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, ALK1278–301 and ALK2233–256, 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 developing future immunotherapeutic options for ALK-positive ALCL patients who fail to respond well to conventional therapies.