Advanced colon cancer is the leading cause of cancer -related death in young American men and the second highest in the world. In the majority of these patients, as cancer progresses it is transformed into the liver. Despite progress in surgical treatments aimed at eliminating cancer, many of these patients will have a relapse of tumor in the liver.
Now, researchers from UC San Francisco (UCSF) have discovered that a new combination of immunotherapy can reschedule the immune environment of colon cancer tumors that spread to the liver. In preclinical models, this treatment often eliminates tumors entirely, offering a possible new course for the treatment of patients with advanced colon cancer.
Their study appears on October 8 Scientific progress.
Since the majority of liver metastasis is resistant to current immunotherapy, our goal was to develop new treatments to strengthen the immune system to recognize cancer and attack it with durability. We have proven that a new combination of immunotherapy can reshape the immune microencard of colon cancer metastases to the liver, often eliminating tumor formation in a preclinical model. ”
Ajay V. Maker, MD, FSS, FSSO, Study of a senior writer, Maurice Galante distinguished professor of surgery, the surgeon of the UCSF Helen Diller Family Cancer leader and the head of surgery oncology at UCSF
Previous surveys have shown unprecedented answers by blocking immune control point in other cancers.However, they have found that the blockade of immune control point (ICB) did not give clinically significant reactions to colon cancer (MSS), which represents more than 95% of colon cancers. These tumors rarely respond to the blocking of the control point only or in combination and studies have shown that ICB response rates in many cancers are lower when there are liver metastases.
To overcome this immunotherapy, the researchers used strategic targeting of specific signals in and around the liver metastases to activate the immune system and to work with MSS tumor control. Their team has previously shown that the over -expression of TNFSF14/Light (signal protein) is associated with elevated tumor (T cells) and improved survival in advanced colon cancer.
In the current study, they invented a model of a mouse of colon liver metastases to prove that light monotherapy activates T cells and intake of immunosuppressive elements that can work with other immunotherapy to control and often kill these tumors.
As colon liver metastases have high levels of CTLA-4 protein receptor expression, the research team combines the over-expression of anti-TLA-4 light, leading to full volume control. The combination of light with anti -ct-4-4-controlled liver metastases of colon cancer by remodeling the microenval of the tumor.
“In this research, we show how our unique strategy can train and reshape immune reactions to both the unique tumors and to resist the repression or timely exhaustion of cancer cells in an established pre -airmill model.” “We are very excited about this work and we are inspired to continue translating the findings to be used in patients.”
Maker adds that they are planning strategies to strategically deliver these immunotherapies directly to the liver and metastatic tumors. Since the anti -CTLA-4 is systematically delivered to patients, it believes that this combined treatment is both translation and particularly feasible.
“This study is a huge step forward in understanding our underlying makeup of these liver metastases and shows that strategic targeting of specific signals can activate our immune system in a way that can kill these tumors,” Maker said.
Source:
Magazine report:
Keenan, BP, et al. (2025). The combined light over -expression and the blockade of control points disturb the environment of the immune environment that affects the metastases of the colon liver. Scientific progress. doi.org/10.1126/sciaadv.Adv9161
