MHC class II-restricted tumor antigens and CD4 + T cells play a role in hematological malignancies as well as solid tumors

Abstract

In my recent review article 1, I chose a topic that not only represents the rapidly moving field of cancer immunotherapy, but also tells an interesting story. The role of CD4+ T cells and MHC class I- and II-restricted antigens (Ags) from solid tumors, especially melanoma, was focused on because: (1) melanoma is the best-studied human tumor model for immunotherapy; and (2) the majority of MHC class II-restricted tumor Ags identified to date are melanoma Ags. The availability of such Ags has led to many clinical trials as well as animal studies. These studies indicate a requirement for CD4+ T cells and MHC class II-restricted tumor Ags for optimal antitumor immunity. By contrast, relatively few tumor Ags from hematological malignancies, such as chronic myelogenous leukemia (CML), have been identified. As a result, I did not cite MHC class II-restricted T-cell peptides from CML in the article, but this was not intended to imply that these MHC class II-restricted peptides are not important. I do not disagree with the comments of Pawelec et al. that MHC class II-restricted Ags or epitopes derived from the fusion proteins BCR–ABL or ABL–BCR are very important. In particular, like the LDFP fusion protein generated by fusing a low-density lipid receptor (LDLR) to a GDP-l-fucose:β-d-galactose 2-α-l-fucosyltransferase (FUT) in an antisense orientation 2, these fusion Ags resulting from chromosomal rearrangement are excellent tumor-specific targets for the immunotherapy of CML. However, the evidence for the other class II-restricted Ags mentioned by Pawelec et al. is not convincing; data on CD4+ T-cell responses to MHC class II-restricted peptides of WT1 were not provided in the original article 3. In addition, defensins appear to function as self-peptides with the ability to bind to MHC class II molecules that inhibit, rather than stimulate, CD4+ T-cell responses 4. Thus, it is not clear if defensins are true MHC class II-restricted tumor Ags.