Most tumors express an array of antigens that act as targets for their immune-mediated destruction, and a number of potential therapies have emerged to exploit this (22). The immunotherapeutic strategy used to induce an immune response against tumors is quite attractive because it offers the potential for a high level of tumor-specific cytotoxicity, minimal side effects, and a durable effect.Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the induction of primary immune responses (29, 33). Because of their central role in controlling cell-mediated immunity, DCs hold much promise as cellular adjuvants in therapeutic cancer vaccines. DC-based immunotherapy has been reported to induce strong antitumor immune responses in animal experiments and in selected clinical trials involving malignant gliomas (2, 11, 36). However, its clinical effects on patients with malignancies have not been up to the expectations because of immune tolerance, the sheer physical burden of tumor antigens, and the mechanisms of tumor escape from the immune surveillance system, among others (10,20).Calreticulin (CRT) acts as a danger signal for DCs, allowing them to phagocytose tumor cells and to prime tumor antigenspecific cytotoxic T cells (CTLs) (12). It was recently reported that CRT exposure on the surfaces of dying tumor cells may determine whether chemotherapy is immunogenic (26). The capacity of chemotherapies to induce immunogenic tumor cell death is associated with the expression of CRT on the tumor cell surface. Furthermore, it was shown with an animal tumor model that the provision of CRT from an exogenous CRT exposure source as enforcement for endogenous CRT exposure could improve the efficacy of chemotherapy by stimulating antitumor immunity (27). Thus, whether chemotherapy triggers such an immunogenic effect depends on the exposure of CRT on the cell surface. The use of multimodality treatments that combine conventional antitumor therapies with immunotherapy, such as vaccination with DC-based vaccines, has emerged as a potentially plausible approach to the treatment of tumors (3, 5). We previously reported that the use of a multimodality treatment regimen with a DC-based vaccine in combination with the chemotherapeutic agent temozolomide (TMZ) leads to enhanced tumor-specific CTL responses and enhanced antitumor effects, resulting in a cure rate higher than that achieved with either a DC-based vaccine or TMZ alone (17,28). However, the immunological factors relating to the antitumor effect of TMZ chemoimmunotherapy in a murine glioma model are still unclear.

These preclinical model results suggest that DC engineered to express IL-12 and pulsed with a tumor lysate could be used in a possible immunotherapeutic strategy for malignant glioma.

No abstract

SummaryAlthough chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)-based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low-dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT-survivin-pulsed DCs enhanced T-cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen-specific immunity appears to be mediated by CD8 + T cells, as determined by in vitro T-cell subset depletion. These studies demonstrated that a combination of low-dose TMZ chemotherapy and TAT-based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.

A 67-year-old man developed swelling of the right leg with inguinal and abdominal pain over a period of 5 days. Excisional biopsy of the left supraclavicular lymph nodes revealed the diffuse, large B cell type of malignant lymphoma. After chemotherapy, he complained of a tingling sensation and weakness in the left upper extremity, and then this progressed to quadriplegia. Electrodiagnostic testing demonstrated the characteristic findings of demyelination, which was consistent with Guillain-Barre syndrome (GBS). Non-Hodgkin's Lymphoma (NHL) leading to GBS, as was observed in the present case, suggests that physicians should be aware of GBS and non-Hodgkin's lymphoma as the full spectrum of these diseaseshas not been fully defined. (Korean J Hematol 2008;43:263-267.)