(Press-News.org)
Advanced colon cancer is the leading cause of cancer-related death in young American men and the second highest worldwide. In the majority of these patients, as the cancer advances it metastasizes to the liver. Despite progress in surgical therapies aimed at eradicating the cancer, many of these patients will have tumor recurrence in the liver.
Now, researchers from UC San Francisco (UCSF), have discovered that a novel combination of immunotherapies can reprogram the immune environment of colon cancer tumors that spread to the liver. In preclinical models, this therapy often eliminated tumors entirely, offering a potential new path for treating patients with advanced colorectal cancer.
Their study appears October 8 in Science Advances.
“Given that the majority of liver metastasis are resistant to current immunotherapies, our goal was to develop new therapies to empower the immune system to recognize the cancer and attack it with durability,” said study senior author Ajay V. Maker, MD, FACS, FSSO, the Maurice Galante Distinguished Professor of Surgery, surgeon-in-chief of the UCSF Helen Diller Family Comprehensive Cancer Center, and chief of Surgical Oncology at UCSF. “We demonstrated that a novel combination of immunotherapies can reshape the immune microenvironment of colon cancer metastases in the liver, often eradicating tumor formation in a preclinical model.”
Previous research has demonstrated unprecedented responses with immune checkpoint blockade in other cancers.However, they have found that immune checkpoint blockade (ICB) did not impart clinically meaningful responses in microsatellite stable (MSS) colon cancer, which represents more than 95% of colon cancers. These tumors rarely respond to checkpoint blockade alone or in combination, and studies have shown that the response rates to ICB in many cancers are lowest when liver metastases are present.
To overcome this immunotherapy resistance, the researchers used strategic targeting of specific signals in and around the liver metastases to activate the immune system and synergize with immunotherapies to control the MSS tumors. Their team previously showed that overexpression of the immunostimulatory cytokine TNFSF14/LIGHT (a signaling protein) is associated with increased tumor-infiltrating lymphocytes (T cells) and improved survival in advanced colorectal cancer.
In the current study, they devised a murine model of colorectal liver metastases to demonstrate that LIGHT monotherapy activates T cells and the recruitment of immunosuppressive elements that can synergize with other immunotherapies to control and often kill these tumors.
As colorectal liver metastases exhibit high levels of protein receptor CTLA-4 expression, the research team combined LIGHT overexpression with anti-CTLA-4, leading to complete tumor control. The combination of LIGHT with anti-CTLA-4 controlled colorectal cancer liver metastases by reshaping the tumor microenvironment.
“In this investigation, we show how our unique strategy can train and remodel immune responses to both recognize unique tumors and resist suppression or early exhaustion of cancer-fighting cells in a well-established pre-clinical model,” said Maker. “We are very excited by this work and are inspired to continue translation of the findings to be used in patients.”
Maker adds that they are devising strategies to strategically deliver these immunotherapies directly into the liver and metastatic tumors. Since anti-CTLA-4 is being delivered systemically in patients, he believes this combination therapy is both translational and highly feasible.
“This study is a huge step forward in our understanding of the 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,” said Maker.
Additional Authors: Bridget P. Keenan, Guilin Qiao, Nicholas Kunda3, Lyonell Kone, Sophia M. Guldberg, Letizia Todeschini, Prabhakaran Kumar, Tommaso Pollini, Sophia Hernandez, Jianzhong Qin, Lawrence Fong, Matthew H. Spitzer, and Bellur S. Prabhakar.
Funding: National Institutes of Health grants R37CA238435, K08CA190855, K12CA260225, and US Department of Defense grants W81XWH-19-1-0457 and HT9425-23-1-0674 (AVM).
About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is a top-ranked specialty hospital, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland; two community hospitals, UCSF Health St. Mary's and UCSF Health Saint Francis; Langley Porter Psychiatric Hospital and Clinics; UCSF Benioff Children’s Physicians; and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit http://www.ucsfhealth.org/. Follow UCSF Health on Facebook, Threads or LinkedIn.
###
END
(Santa Barbara, Calif.) — The trade of totoaba has all the intrigue of a crime thriller. Dollars and drugs change hands as a criminal cartel vies against the government. Communities and endangered species are caught in the crosshairs of a lucrative illicit trade. It may then come as a surprise that the totoaba is a fish.
The totoaba is a large, yet unassuming, species of fish native to the Gulf of California. But its mundane appearance belies incredible value on the black market. “Totoaba swimbladder can sell for up to $80,000 USD per kilogram ...
When the Norwegian company that manufactures the Safeback SBX device which is already on the market, approached Eurac Research to have it independently tested, it was clear that the international research team led by physician and researcher Giacomo Strapazzon would publish the results of the study in any case, regardless of the outcome.
For the researchers, the experiment posed a significant challenge, as many participants were completely buried in snow, raising concerns that over two-thirds might require urgent excavation. The volunteer group – composed entirely of enthusiastic ski mountaineers, roughly half of them women – ranged from ...
Acute or short-lived pain, despite its bad reputation, is usually a lifesaver. It acts as a transient negative sensory experience that helps us avoid danger. Touch a hot stove, stub a toe, or bonk your head on a low branch, and the nervous system cues up an “Ow!” Over time, the sting fades, the wound heals, but the lesson sticks.
Chronic pain is different; the alarm keeps blaring long after the fire is out, and then the pain itself becomes the problem. Nearly 50 million people in the United ...
According to a study by researchers at the Universitat Oberta de Catalunya (UOC), time-restricted feeding can have a positive impact on athletes in terms of both their health and performance. The effects of time-restricted eating – where food intake is permitted within a restricted window ranging from 3-4 to 10-12 hours – have been widely studied in the general population, where they have been shown to increase life expectancy, but there is little evidence on its positive effects on high-performance athletes.
The study – "Effect of time-restricted feeding ...
New Curtin University research has found the impact of bushfires and prescribed burns on global bee populations is highly varied, with some species benefiting from fire while others face severe risks.
The study, led by Adjunct Research Fellow Dr Kit Prendergast from Curtin’s School of Molecular and Life Sciences, examined 148 studies from around the world to understand how fire impacts bees.
The review considered the severity, frequency and duration of fires, along with the different characteristics of bees, such as where they ...
Forming sustainable research partnerships with Indigenous peoples requires trust and mutual benefit, say microbiome researchers in an opinion paper publishing October 8 in the Cell Press journal Trends in Microbiology. The paper presents a framework for building this type of relationship based on insights from the team’s 15-year-long collaboration with the Matsés, a group of people who live in the Amazon rainforest on the border of Peru and Brazil. To build trust, the researchers worked in collaboration with the Matsés through all stages of the research project, from developing research methods to disseminating results.
“Establishing genuine partnerships with ...
Engineered polymers hold promise for use in next generation technologies such as light-harvesting devices and implantable electronics that interact with the nervous system – but creating polymers with the right combination of chemical, physical and electronic properties poses a significant challenge. New research offers insights into how polymers can be engineered to fine-tune their electronic properties in order to meet the demands of such specific applications.
“Silicon-based electronics have been around for decades, and we have a thorough understanding of the electronic properties of materials used in those technologies,” says Aram Amassian, co-corresponding author of ...
New research has revealed that about 90 percent of marine aquarium fish sold by online retailers in the United States are sourced directly from wild populations, mostly in the western Pacific and Indian Ocean. With the US accounting for around two-thirds of all global aquarium fish imports, researchers warn that this reliance on wild capture threatens the sustainability of coral reef ecosystems and puts endangered and threatened species at greater risk of extinction.
The research, led by postdoctoral research associate Dr Bing Lin from the University of Sydney’s Thriving Oceans Research Hub in the School of Geosciences, analysed data from four major US-based online aquarium ...
About The Study: Current minimum case volume standards for complex surgical procedures, based on older volume outcome studies, do not align with contemporary practice. These findings demonstrate that volume-outcome curves have changed, with fewer cases needed to meet benchmark 30-day mortality over time.
Corresponding Author: To contact the corresponding author, Nabil Wasif, MD, MPH, email wasif.nabil@mayo.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jama.2025.17274)
Editor’s Note: Please ...
A new study led by researchers at the Department of Population Medicine - Harvard Pilgrim Health Care Institute, Boston Medical Center, and Boston University School of Public Health finds that how Medicaid programs are designed can make a big difference in the care pregnant and postpartum people receive.
The study, “Medicaid Accountable Care Model Designs and Maternal Health Measures”, was published October 8 in JAMA Network Open.
Maternal health care in the U.S. is in crisis. There is an urgent need to identify models of care that may improve maternal health outcomes, especially ...
