Introduction  Colorectal cancer is the third most common cancer worldwide, with about 15% of these tumours related with microsatellite instability, which confers distinct characteristics to these tumours, both clinicopathological and in the response to treatments. In fact, the poor response to chemotherapy in these tumours has led to the investigation for new treatments, with immunotherapy being the most successful one to date. The focus of this review is to assess the response of microsatellite unstable colorectal cancer to PD-1 blockade, and the mechanisms behind that response. Methods  A PubMed research was conducted, resulting in the inclusion of 47 articles in this review. Results  Microsatellite instability results in a high neoantigen load, leading to a highly active immune microenvironment of the tumour, mainly due to T-cells. To counteract this, there is an upregulation of PD-1, acting as a “brake” for immune cells, facilitating tumour growth and metastasis. This upregulation makes these tumours great candidates for treatment with PD-1 blockade, as seen in many clinical trials, where the overall responses and progression free survival rates were higher than those observed in microsatellite stable tumours. Conclusion  With the importance of colorectal cancer with microsatellite instability new treatments are necessary. Therefore, PD-1 blockade is a promising treatment for colorectal cancer with microsatellite instability, with improvement in survival rates and a better prognosis for these patients.

Colorectal cancer is one of the most common tumours in the world, with microsatellite instability having an important role in the development of these tumours. Microsatellite instability is responsible for the worse response of tumours to chemotherapy, while also having a role in the better prognosis associated with these tumours. This relates to the higher immune infiltration that results from the high neoantigen load of microsatellite unstable tumours. This highly responsive immune microenvironment seen in microsatellite unstable colorectal cancer makes these tumours great candidates for therapies targeting the immune system, such as immune checkpoint inhibitors. The PD-1/PD-L1 axis is upregulated in colorectal cancer with microsatellite instability, making the blockade of this axis a good therapy alternative for these patients.Pembrolizumab has shown to be an effective PD-1 blocker, with trials showing good responses to this therapy, as seen in the most recent KEYNOTE-177 trial. Conclusion:Colorectal cancer with microsatellite instability is a subtype of tumour with characteristics making it a great candidate for the treatment with immunotherapy, namely with the PD-1 blocker pembrolizumab, enhancing the importance of including this treatment in the options available for these patients.