Predictors of immunotherapy benefit in patients with microsatellite stable metastatic colorectal cancer

Introduction: Colorectal cancer (CRC) is the second most common cancer. Once metastatic, patients are generally incurable and receive treatment to prolong survival. Immunotherapies use a patient's immune system to attack their cancer. These treatments are effective in CRC patients with microsatellite instability (MSI). Unfortunately, 95% of patients lack MSI and are called microsatellite stable (MSS). This group usually doesn't respond to immunotherapy and we need to explore why.

Specific Aims:  

We aim to identify:

  1. why some MSS patients benefit from immunotherapy, and  
  2. what can we target to activate immune cells in patients who don't respond to immunotherapy.  

Methods: We will investigate how the immune system and tumors interact in patients from two clinical trials. These trials evaluated immunotherapy in MSS CRC. Blood and tumor samples from these trials will be tested to identify features that predict response. These results will then guide the creation of new clinical trials with immunotherapy for CRC using our findings.  

Significance: Immunotherapy does not work for the 95% of CRC patients who are MSS. We will identify how to activate the immune system in CRC patients with MSS so they too can benefit from immunotherapy.