Abstract
Patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) mount a humoral and cellular immune response against ALK. More than 90% of children and adolescents with ALK-positive ALCL have detectable anti-ALK antibodies in serum or plasma, and the antibody titer inversely correlates with the risk of relapse. ALK-specific CD8 and CD4 T cell responses have been described in patients with ALK-positive ALCL. Vaccination with ALK DNA led to protection against lymphoma growth in a murine model. Collectively, these data suggest that the ALK-specific immune response is involved in the control of the disease. The characteristics of the humoral and cellular immune response against ALK as well as tumor immune escape mechanisms have been increasingly investigated. However, tumor and host factors contributing to the individual immune response against ALK are still largely unknown. Depending on the individual strength of the immune response and its determinants, individualized immunological approaches might be appropriate for the consolidation of ALCL patients. Strategies such as ALK vaccination could be effective for those with a pre-existing anti-tumor immunity, while an allogeneic blood stem cell transplantation or check-point inhibition could be effective for others.
Highlights
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a biologically defined disease of children and young adults [1]
Autoantibodies against ALK might not have direct anti-tumor activity but rather represent a surrogate marker for the ALK-specific T cell response. This is supported by the observation that the vaccination of B cell-deficient BALB/C mice with ALK plasmid DNA showed a protection against tumor growth and a cytotoxic T cell response after challenge with ALK-positive lymphoma cells [53]
The increasing evidence for the existence and clinical relevance of an autologous immune response against ALK implies that immunotherapeutic approaches might be an effective therapeutic intervention for the treatment of ALK-positive ALCL patients
Summary
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a biologically defined disease of children and young adults [1]. The histological subtype of ALCL is independently associated with the risk of relapse [10,34,36] and the bystander infiltrate as well as the surface marker expression on ALCL cells differ according to the subtype [35] These observations collectively hint towards a cellular immune interaction between bystander cells and tumor cells. Among ALK-positive ALCL patients, the serum concentration of the pro-inflammatory cytokines IL-6, IFN-γ, IP-10, and sIL-2R correlates with the clinical and biological characteristics as well as the risk of relapse. This suggests that ALCL cells might influence the immune system of patients, leading to a different outcome [39]
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