Editorial [Hot Topic: Immunotherapy of Cancer (Guest Editors: Ezra E.W. Cohen and Nikolai G. Rainov)]

The current hot topics issue of RRCT focuses on immunotherapy of cancer, a field that seems to offer promises as the new, biological dimension in cancer treatment, but it is still in his early days. Immunotherapy involving interferons and monoclonal antibodies has now become part of standard cancer treatments and is considered the fourth pillar of therapy, beyond surgery, chemotherapy, and radiation therapy. Other types of immunotherapy, such as cancer vaccines, still remain experimental. Although quite a few clinical trials of new immunotherapy paradigms are in progress, a large quantity of work remains to be done before the findings and conclusions can be widely applied in the clinical routine. The first article in this hot topic issue by Rainov, Gorbatyuk, and Heidecke reviews treatment of malignant glioma, focusing on ligand-conjugated toxins. The authors discuss the rationale for such approaches, utilization of different ligands, and promising early clinical trials. These therapies offer the ability to target malignant cells in a disease that is almost universally refractory to conventional therapy. The article on dendritic cell (DC) immunotherapy for malignant glioma by Luptrawan, Liu, and Yu discusses the results of DC-based immunotherapy clinical trials and explores the future use of DC vaccines for glioma immunotherapy. The prognosis for patients with malignant gliomas is poor. It has remained almost unchanged in the last decades, despite considerable advances in surgical technology, chemotherapy and radiation therapy. Immunobiological paradigms are thus being increasingly explored as an adjunct to standard therapies. In recent clinical trials, DC have demonstrated an ability to promote an effective anti-tumor immune response and to sensitize glioma cells to chemotherapy. The challenge with such vaccination strategies is to break the immune tolerance, so that the patient's immune system will recognize cancer cells. The success of vaccines depends on the identification of appropriate tumor antigens, establishment of effective immunization strategies, and the ability to circumvent inhibitory immune mechanisms. The authors state in their review that in the future the fundamental knowledge of DC immunobiology, tumor immunology and cancer biology needs to be significantly extended, and that new findings must be implemented in the rational design of DC-based cancer immunotherapy. The review by Rodriguez and Gutierrez focuses on an approved agent in the treatment of lymphoma and highlights specific aspects of the pharmacokinetics and pharmacodynamics of the agent that are not always appreciated or have recently come to light. These factors influence toxicity and efficacy of the agent and should be taken into account when administering the drug and are certainly worthy of further study. In their review on immunotherapy of hepatocellular carcinoma (HCC), Greten, Manns, and Korangy deal with the fifth most common cancer worldwide, which has an increasing incidence in the Western world. A number of experimental trials, many of them immunotherapeutic, have been performed in patients with HCC, mainly because systemic chemotherapy has failed to show substantial benefits. The authors review recent immunotherapy trials in HCC and point at promising strategies to be explored in more detail in the near future. We hope that this “Hot Topic Issue” offers interest to readers in a field of cancer care that is in its early stages therapeutically, but has the potential to truly change the natural history of this disease. There is a plethora of immunologic applications being explored in cancer research and the four review articles in this issue highlight some of the most promising ones.