The Immune Response to Class I-Associated Tumor-Specific Cutaneous T-Cell Lymphoma Antigens

Abstract

In order to determine whether the neoplastic T cells from patients with cutaneous T-cell lymphoma express tumor-specific antigens that can serve as the targets of an immune response, we took advantage of family-specific monoclonal antibodies, magnetic bead technology, and recombinant cytokines, which provided the previously precluded ability to isolate and expand populations of purified tumor and autologous CD8 cytotoxic T cells. Four patients with advanced cutaneous T-cell lymphoma had CD8 cells that specifically killed autologous tumor in a class I limited fashion. Tumor cell cytolysis could be specifically enhanced by pre-culture with autologous gamma-irradiated tumor. The cytolytic T cells produced tumor necrosis factor-alpha in response to stimulation with autologous tumor. The presence of tumor-specific cytotoxic T cells recognizing distinctive class I associated molecules on cutaneous T-cell lymphoma tumor cells suggests that infiltration of early lesions by CD8 cells reflects host immunity to the neoplasm. These studies provide the foundation for the development of tumor vaccines through the use of cytotoxic T cells to isolate and characterize tumor-associated cutaneous T-cell lymphoma peptides.

A lymphocyte cell surface heat shock protein homologous to the endoplasmic reticulum chaperone, immunoglobulin heavy chain binding protein BIP

“…Previous studies (Berger et al, 1996) demonstrated that a functional tumor-specific cytolytic class I-restricted T-cell response can be identified in vitro in certain CTCL patients. The target for this response appears to be tumor-associated peptides presented in class I MHC molecules.…”

“…The demonstration that CTCL lymphocytes express distinctive, class I major histocompatibility complex-associated tumor-specific antigens that can be recognized by autologous CD8 cytotoxic T cells (in patients responding to immunotherapeutic photophoresis) suggests that cell surface molecules on CTCL lymphocytes may serve as tumor-specific immunogens (Berger et al, 1996).…”

HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas

“…3,4 Most of the abnormalities might be attributed to the pleiotropic immunosuppressive effects of interleukin-10 (IL-10), as demonstrated in different CL types. [5][6][7][8] Despite the evidence of antitumor humoral and cell-mediated immune response in CL, [9][10][11] the disease may evolve further, eventually killing the patient. Besides the production of immunosuppressive cytokines, alterations of HLA class I status responsible for the presentation of tumor peptides to T cells could be the reason for an ineffective antitumor response.…”

CD4+ cutaneous T-cell lymphoma cells express the p140–killer cell immunoglobulin-like receptor

“…Thus, in cutaneous lesions, it is difficult to distinguish CD4 ϩ CTCL cells from reactive infiltrating CD4 ϩ T lymphocytes. [4][5][6] We previously reported a unique CD4 ϩ T-cell line derived from CTCL lesions. 6 We demonstrated that the cell line and the in vivo tumor cells expressed an identically sized, complementarily determining region 3 of T-cell receptor (TCR)-V␤ transcripts.…”