Smitha Krishnamurthi, MD

Taussig Cancer Institute


Impact Award

Identification of Early Stage Colon Cancer Patients with Promise for Immune Checkpoint Inhibitor Response

If our immune system can recognize cancer as foreign and fight it, that could lead to cure even in patients with advanced cancer. Drugs that activate the immune system have markedly increased the lifespan of people with melanoma and lung cancer, even when it is widespread (metastatic). For patients with metastatic colorectal cancer, however, these immunotherapy drugs only work in the 5% with a rare type of cancer called MSI-high. It is critical that researchers figure out how to make these drugs work for patients with the usual type of colon and rectal cancers.

Because immunotherapy does not work for metastatic usual-type colon cancer, it was assumed it would not work for early stage usual-type colon cancer. A small Dutch study boldly treated patients with early stage usual-type colon cancer with two immunotherapy drugs before surgery. Surprisingly, after the treated cancers were removed by surgery, the cancer was gone or almost gone in 4 out of 15 specimens. Immunotherapy therefore can work in some early stage usual-type colon cancers. It may be that the immune system is better able to recognize early stage colon cancer compared to when it has spread.


Standard immunotherapy is ineffective against microsatellite stable (MSS) metastatic colorectal cancer, but small studies suggest it may benefit patients with early stage colon cancer. This project will look for differences in activation of the immune system in stage IIb/III MSS colon cancer versus liver metastases, which are known to be immunosupressive. If stage IIb/III MSS colon cancers have a higher density of cytotoxic T cells and elevated expression of pathways associated with effector T cell function compared to MSS liver metastases, that would support a clinical trial of immunotherapy to increase cure rates for patients with stage IIb/III MSS colon cancer.