Why Colon Cancer Is Largely Unresponsive to Immunotherapy

Colorectal cancer is the third-most common type of cancer among adults in the United States, affecting an estimated 106,970 people in 2023 and predicted to take more than 50,000 lives this year. Treatment often involves surgery to remove as much of the tumor as possible, followed by chemotherapy and radiation therapy to kill off any remaining tumor cells.

Recent research published in the “Nature Genetics” journal has shed new light on why immunotherapy, a relatively new type of cancer treatment that uses a patient’s own immune system to kill cancer cells, isn’t as effective against colon cancers. Researchers studied the effects of immunotherapies on mice suffering from DNA mismatch repair deficiency (MMrd), a condition that renders the body unable to repair DNA replication errors and increases susceptibility to cancers.

MMrd can encourage the proliferation of cancer cells, causing them to aggressively mutate and resulting in a high tumor mutation burden (TMB) in patients diagnosed with colon cancer. Although conventional wisdom states that mutations generated by MMrd should give rise to new antigens and trigger stronger immune responses against tumors, recent research proved that this isn’t always the case.

Cold Spring Harbor Laboratory Cancer Center member and assistant professor Dr. Peter Wescott said the team discovered that colon cancers were not immunogenic across the board, questioning conventional knowledge and potentially opening the door to alternative colon cancer treatments. Wescott described tumors with TMB as shrubs or bushes that have numerous branches growing in different directions.

Although the tumors have several mutation sets of their own, Wescott explained that the tumor cells rarely share any mutations, meaning using samples from the tumor to identify mutations cannot give a full and accurate profile of tumor mutations. Different cells from different regions of the tumor will have numerous mutations but will share few, if any, mutations across the board. The result of these diverse mutations is that tumors with high TMB rarely trigger large immune responses from the body, making them much less likely to respond positively to immunotherapy.

The research team also discovered that mice that had shared clonal mutations reacted well to immunotherapy compared to mice having subclonal mutations that were shared by only certain cancer cell subsets, strengthening the theory that disparate mutations in colon cancer may reduce the effectiveness of immunotherapy. Wescott says the team may have discovered a biomarker that could help physicians determine whether patients will respond to immunotherapy.

Entities such as Renovaro BioSciences Inc. (NASDAQ: RENB) are also exploring gene and cell therapy as ways to halt or even reverse the progression of various cancers. These treatment approaches could be viable alternatives in cases where immunotherapy hasn’t been efficacious.

NOTE TO INVESTORS: The latest news and updates relating to Renovaro BioSciences Inc. (NASDAQ: RENB) are available in the company’s newsroom at https://ibn.fm/RENB

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