This E-Learning module provides multiple learning opportunities. The author first presents the theoretical background needed to understand basics in cancer immunotherapy and subsequently provides an overview of the immunobiology of colorectal cancer (CRC), as well as therapeutic immune strategies in CRC patients with microsatellite instable (MSI) and microsatellite stable (MSS) tumours. The discussed therapeutic strategies are supported by evidence from the clinical trials testing immune checkpoint inhibitors, adoptive cell therapies, anti-tumour vaccines and other agents.
When considering treatment with immune checkpoint inhibitors, it is important to discriminate between MSI and MSS CRC. Alterations on the microsatellite repairing system can be determined by PCR against a group of microsatellites looking for mutations and by immunohistochemistry looking for the expression of the different mismatch repair genes. The overlap between both techniques is 90%.
The author underlines a theoretical basis for an improved clinical benefit of treatment with checkpoint inhibitors in case of MSI CRC. Anti-PD1 axis monoclonal antibodies produce a dramatic and long-lasting response in MSI CRC and represent the new standard of care in the United States. Current research efforts aim to move the treatment to earlier lines and increase the percentage of patients who respond to treatment. It is expected that a combination of anti-CTLA4 and anti-PD-1 agents will soon become a new standard of care.
However, the other aspect to consider is that the research efforts in MSS CRC, in particular immune checkpoint inhibitors and MEK-based combinations, have failed in MSS metastatic CRC, potentially reflecting the lack of implementation of tumour biology knowledge into study design. A new generation of promising compounds and combinations, specifically designed for this disease, are currently entering into clinical development. The author underlines that a deeper understanding of the tumour biology is crucial to ensure their success and further implementation in clinical practice.
This E-Learning Module provides an excellent summary of immunotherapy advances emerged in a subset of patients with molecularly defined advanced CRC. The author provides an outlook in the field by discussing opportunities such as potentials from moving the treatment to earlier settings and maximising the percentage of responding patients, should the marketing authorisation for immune checkpoint inhibitors be granted for this indication in Europe.
In terms of outlook for the future, the author also emphasises that personalised immune therapies can be good options for patients not responding to other available therapies. However, their complexity makes these options only available in highly experienced centres, since their success depends on the experience of the team.
