Recent Advances in Cancer Immunotherapy

Cancer immunotherapy is designed to activate and up-regulate the host immune responses against tumor cells and is currently in use or under investigation for cancer treatments. Although tumor cells can use a variety of mechanisms to create an immunosuppressive environment, many agents and strategies to reduce or eliminate tumor-induced immune suppression are either being developed or already in clinical trials. This review deals with recent advances in cancer immunotherapy, focusing on new strategies to enhance antitumor immunity. Numerous approaches have been tested for the development of therapeutic cancer vaccines. Recently, several promising reports suggest that clinical benefit has been shown in randomized phase III trials for vaccines against prostate cancer, follicular lymphoma, and melanoma. Moreover, in 2010, the first patient-specific immunotherapy (sipuleucel-T) was approved by the FDA for the treatment of prostate cancer. On the other hand, some chemotherapeutic agents such as cyclophosphamide and docetaxel, have direct effects on the immune system that is likely to contribute to an improved antitumor immunity. Therefore, cancer immunotherapy combined with chemotherapy may represent one approach for breaking tumor-induced immune suppression. To date, a number of monoclonal antibodies are in use or under evaluation. Among these antibodies, blocking negative immunoregulatory receptors, CTLA-4 and PD-1, also represent a new strategy to induce antitumor immunity by manipulation of the immune system. In clinical trials, these antibodies could increase anti-tumor T-cell immunity and result in objective tumor regression in some patients. Thus, accumulating data from recent cancer vaccine trials, the manipulation of immune suppression using chemotherapeutic agents, and the use of immune-stimulatory antibodies raise the hope that immunotherapy could become the fourth modality of cancer treatment. Based on these new findings, in our hospital, a clinical trial using dendritic cells combined with low dose cyclophosphamide and docetaxel in patients with relapsed and refractory head and neck squamous cell carcinoma is under way (UMIN000003725, ClinicalTrials.gov identifier, NCT01149902). In the near future, various immunotherapeutic modalities will most probably be applied as novel approaches in the treatment of head and neck cancer.