Combinatorial Immunotherapies for Metastatic Colorectal Cancer

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion-forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.