Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives

Curr Colorectal Cancer Rep. 2015 Jun 1;11(3):125-140. doi: 10.1007/s11888-015-0269-2. Epub 2015 Jun 29.

Abstract

Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although, many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized antitumor immune cells against malignancies, nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy - of which benefit less than 10% of those receiving therapy. After decades of progress, however, new insights into the mechanisms of immunosuppression, tolerance, and mutation profiling established novel therapies that circumvent these immunological barriers. This review underlines the most exciting methods to date that manipulate immune cells to curb mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint inhibitor antibodies - of which hint at effective and enduring protection against disease progression and undetected micrometastases.

Keywords: Adoptive Immunotherapy; Adoptive T-cell therapy; Allogeneic stem-cell transplant; Antibody therapy; Antitumor immunity; Biomarker; CTLA-4; Cytotoxic T-Lymphocyte; Dendritic cell; Helper T-Cell; Immunosuppression; Immunosurveillance; Immunotherapy; Ipilimumab; Macrophage; Metastatic colorectal cancer; Myeloid-derived suppressor cell; PD-1/L1; Regulatory T-cell; T-cell; Vaccine.