Mikio Kajihara, Kazuki Takakura, Tomoya Kanai, Zensho Ito, Keisuke Saito, Shinichiro Takami, Toshifumi Ohkusa, Shigeo Koido, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine (Kashiwa Hospital), Kashiwa, Chiba 277-8567, Japan
Shigetaka Shimodaira, Cell Processing Center, Shinshu University Hospital, Nagano 390-8621, Japan
Masato Okamoto, Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan
Toshifumi Ohkusa, Shigeo Koido, Institute of Clinical Medicine and Research, the Jikei University School of Medicine, Chiba 277-8567, Japan
Author contributions: Kajihara M, Takakura K, Kanai T, Ito Z, Saito K, Takami S, Shimodaira S, Okamoto M, Ohkusa T and Koido S designed the study; Koido S wrote the paper; Kajihara M, Takakura K and Koido S contributed equally to this manuscript.
Supported by Grants in Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
Conflict-of-interest statement: No potential conflicts of interest were disclosed by any of the authors.
Correspondence to: Shigeo Koido, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine (Kashiwa Hospital), 163-1 Kashiwashita, Kashiwa, Chiba 277-8567, Japan. shigeo_koido@jikei.ac.jp
Telephone: +81-4-71641111 Fax: +81-4-71633488
Received: February 11, 2016 Peer-review started: February 11, 2016 First decision: March 7, 2016 Revised: March 15, 2016 Accepted: April 7, 2016 Article in press: April 7, 2016 Published online: May 7, 2016 Processing time: 77 Days and 21.1 Hours
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.
Core tip: Dendritic cell (DC) is potent antigen-presenting cells that play a pivotal role in the induction of antitumor immune responses. Strategies for delivering antigens to DCs have been developed and used in clinical trials in cancer patients, including colorectal cancer (CRC). Numerous reports indicate that the use of DC-based immunotherapy for CRC patients is promising to induce antigen-specific CTL responses. However, the immune suppression induced through CRC and the tumor microenvironment continues to be a major hurdle. Thus, the combination of DC-based immunotherapy with immune-modulating agents may be necessary to maximize antitumor immunity. These combinatorial therapies may have the potential for clinical benefit.
