For the vast majority of patients fighting colorectal cancer, immunotherapy—one of the most promising frontiers in oncology—has remained an elusive option. While these treatments can trigger the immune system to destroy malignant cells, they currently work for only a minor fraction of patients, often leaving clinicians to guess who will respond and who will not.
A new study from researchers in Spain has identified a specific protein biomarker that could fundamentally change this selection process. By detecting the presence of CTHRC1-positive cancer-associated fibroblasts (CAFs), doctors may soon be able to predict with greater accuracy which patients will benefit from immunotherapy, potentially expanding the reach of these life-saving treatments beyond the current narrow eligibility window.
Currently, immunotherapy is applicable to only around 5% of patients with colon and rectal cancer, and even within that group, the results are inconsistent. The discovery of the CTHRC1 biomarker offers a window into the “cold” tumor microenvironment—the protective shield that cancers build around themselves to hide from the immune system—allowing physicians to identify patients who were previously considered ineligible for these therapies.
Dr Eduard Batlle
Image source: Hospital del Mar Research Institute
Decoding the tumor microenvironment
The success of immunotherapy depends less on the cancer cells themselves and more on the ecosystem surrounding them. This “tumor microenvironment” consists of blood vessels, immune cells, and stromal cells that can either help the body fight the disease or help the tumor grow.
Central to this process is a cytokine called TGF-beta. In many cancers, high levels of TGF-beta act as a signal that suppresses the immune response and promotes treatment resistance, leading to poorer disease outcomes. The research team found that CTHRC1 is a factor induced by TGF-beta, meaning the presence of this protein serves as a measurable indicator of the cytokine’s activity.
“The tumour microenvironment plays a decisive role in the progression of colorectal cancer and in its response to treatments. Over the years, our research has shown that TGF-beta is a key regulator of this ecosystem, modulating the behaviour of stromal cells surrounding the tumour. The identification of CTHRC1 as a TGF-beta-induced factor exemplifies how basic research can lead to clinically applicable biomarkers,” states Dr Eduard Batlle, ICREA researcher at IRB Barcelona and member of CIBERONC.
By identifying CTHRC1(+) CAFs, researchers can determine the state of the immune cells within the tumor and assess their actual ability to attack neoplastic cells. This provides a biological map that tells oncologists whether the patient’s immune system is being actively blocked or if it is primed for a response.
From the lab to the pathology ward
A common hurdle for new medical discoveries is the “implementation gap”—the time it takes for a complex laboratory discovery to become a usable tool in a community hospital. However, this biomarker is uniquely positioned for rapid adoption because it can be detected using immunohistochemistry (IHC) tests.
IHC is a standard diagnostic technique used to visualize specific proteins in tissue samples. Because these tests are already routinely available in almost every hospital pathology service, integrating CTHRC1 screening would not require expensive new machinery or specialized infrastructure.
Dr Mar Iglesias, first author of the study and Head of the Pathology Department at Hospital del Mar, notes that this accessibility is a cornerstone of the discovery’s value. She explains that “the results position CTHRC1(+) CAFs as a useful marker with the potential to be integrated into routine clinical practice in our services and hospitals, thereby helping to guide the selection of the most appropriate treatment for each patient.”
This shift toward precision oncology means that instead of a one-size-fits-all approach, therapeutic strategies can be tailored to the specific molecular signature of a patient’s tumor. Dr Clara Montagut, Head of Section of the Medical Oncology Department at Hospital del Mar, notes that “this biomarker improves the selection of patients who could potentially benefit from immunotherapy,” which in turn helps guide more effective therapeutic strategies for colorectal cancer patients.
Broader implications for oncology
While the primary focus of the study was on colon and rectal cancers, the biological mechanisms involving TGF-beta and CTHRC1 are not exclusive to the digestive system. The researchers suggest that this biomarker could potentially be applied to other “cold” tumors that typically resist immunotherapy, including breast and lung cancers.
The study also opens a new door for drug development. Because high levels of the CTHRC1 protein are linked to treatment resistance, the protein itself could become a target. Developing inhibitors that block CTHRC1 could potentially “unlock” the tumor microenvironment, making previously resistant cancers susceptible to immunotherapy.
| Feature | Current Standard | With CTHRC1 Biomarker |
|---|---|---|
| Patient Eligibility | Limited to ~5% of patients | Potential to identify more eligible candidates |
| Testing Method | Variable genetic/protein markers | Routine immunohistochemistry (IHC) |
| Predictive Value | General response rates | Specific assessment of immune cell activity |
| Therapeutic Goal | Broad immunotherapy application | Precision selection and potential CTHRC1 inhibition |
The research was supported by several organizations, including the Spanish Association Against Cancer (AECC), highlighting the collaborative effort between academic research and patient advocacy groups to move the needle on cancer survival rates.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Patients should consult with their oncology team to discuss treatment options and eligibility for clinical trials or specific biomarkers.
The next phase for this research involves further clinical validation to establish standardized thresholds for CTHRC1 levels across larger, more diverse patient populations. These results will be critical in determining how the marker is integrated into official clinical guidelines for colorectal cancer care.
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